bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Background

Since 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.

Methods

After 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.

Results

Of 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.

Conclusions

In 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

Introduction

Cryptococcal 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.

Methods

Clinical 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.

Results

Of 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.

Conclusions

Acute 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

Introduction

Recent 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 Methods

A 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.

Results

One 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.

Conclusions

Significant 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

Introduction

In 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 Methods

Prospective 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.

Results

Out 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%).

Conclusions

The 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

Introduction

We 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 Methods

Patients 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.

Results

One 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.

Conclusions

In 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

Introduction

Daclatasvir (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 Methods

An 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.

Results

Subjects 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.

Conclusions

Steady‐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

Introduction

Factors 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).

Methods

The 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.

Results

SVR 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).

Conclusions

Along 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

Introduction

Several 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 Methods

Observational 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.

Results

A 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).

Conclusions

In 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.
Acute hepatitis C virus (HCV) infection in the setting of HIV coinfection: a single‐centre 10‐year follow‐up
Authors: Ingiliz Patrick , Steininger Katharina , Schuetze Marcel , Dupke Stephan , Carganico Andreas , Krznaric Ivanka , Wienbreyer Andreas , Baumgarten Axel
Published: November 2014

Introduction

Acute hepatitis C virus (HCV) infection has emerged as a major cause of morbidity in the HIV‐infected population. Most guidelines recommend early treatment with pegylated interferon and ribavirin due to higher cure rates. The impact of acute HCV and its treatment on the outcome of the HIV‐infected population is unknown. With new treatment options for HCV, early treatment of acute HCV has to be questioned. Here, we report a long‐term analysis on patients with acute HCV.

Methods

Retrospective analysis from an outpatient clinic from Berlin. All patients with the diagnosis of acute HCV according to The European AIDS Treatment Network (NEAT) criteria were included in the database at their date of HCV diagnosis and followed‐up until the last medical contact. Demographic data was taken from the medical file. A fibrosis estimation was performed using transient elastography (Fibroscan(®). A Fibroscan value above 7 kPa was considered as significant fibrosis, above 12.4 kPa as liver cirrhosis. The following outcomes were documented: (a) liver‐related: hepatic decompensation, cirrhosis, hepatocellular carcinoma. (b) non‐liver‐related: death, myocardial infarction, AIDS‐defining event, psychiatric hospitalisation.

Results

A total of 207 cases of acute HCV infection in HIV‐infected patients were diagnosed between May 2002 and September 2013. All patients were male and declared homosexual contacts as their risk factor for having acquired HIV. The mean age was 39 years, 162 patients (78%) were on antiretroviral treatment, and the median CD4 cell count was 593/mm3 (IQR 443–749). At HCV diagnosis, the highest median alanine aminotransferase (ALT) level was 408 IU/mL (159–871), the HCV viral load was 800,000 IU/mL (45x103–2.8x106). 22 cases (11%) cleared their infection spontaneously, 161 (77%) underwent interferon‐based treatment. Of those treated, 58% had a sustained virological response. 36 cases of HCV reinfection were documented. All patients were followed‐up over an interval of 806 patient‐years. The median liver stiffness was 5.3 kPa (4–7) after a median interval of 34 months. 33 patients developed significant fibrosis, and 11 patients (6%) developed cirrhosis. Nine (5%) patients died during follow‐up, and 11 developed non‐liver‐related endpoints. All but one deceased patients had interferon‐based treatment.

Conclusions

Severe hepatic disease and death rarely occurs in a highly treated HCV population. As interferon‐based treatment may induce side effects, it is from now on justified to await new HCV treatment options.
Central nervous system penetration‐effectiveness rank does not reliably predict neurocognitive impairment in HIV‐infected individuals
Authors: Libertone Raffaella , Lorenzini Patrizia , Balestra Pietro , Pinnetti Carmela , Ricottini Martina , Maddalena Plazzi Maria , Menichetti Samanta , Zaccarelli Mauro , Nicastri Emanuele , Bellagamba Rita , Ammassari Adriana , Antinori Andrea
Published: November 2014

Introduction

Central nervous system (CNS) penetration‐effectiveness (CPE) rank was proposed in 2008 as an estimate of penetration of ARV regimen into the CNS, and validated as predictor of CSF HIV‐1 replication. Results on predictive role of CPE on neurocognitive and clinical outcome were conflicting.

Materials and Methods

Retrospective, cross‐sectional analysis of neurocognitive profile in HIV‐infected cART‐treated patients. All patients underwent neuropsychological (NP) assessment by standardized battery of 14 tests on 5 different domains. People were classified as having NCI if they scored >1 standard deviation (SD) below the normal mean in at least two tests, or >2 SD below in one test. Linear and logistic regression analyses were fitted using as outcome Npz8 and impaired/not impaired respectively.

Results

A total of 660 HIV‐infected cART‐treated individuals from 2009 to 2014, contributing a total of 1003 tests (mean age 49 (IQR 43–56), male 82%; median current CD4 586/mm3; 18% HCV infected; HIV‐RNA <40 cp/mL in 84%). Current ARV regimen was 2NRTIs+1NNRTI 50.3%, 2NRTI+1PI/r in 32.6%, NRTI sparing in 11.1%. Mean CPE of current regimens was 6.6 (95% CI 6.5–6.7). As per test multivariable analysis, higher CPE values were associated to poor NP tasks (Beta=−0,09; 95% CI −0,14 −0,03; p=0.002 at multivariable linear regression). The association between higher CPE and increased NCI risk was confirmed at multivariable logistic regression, with a 1.24‐fold risk of NCI occurrence for each point increase of CPE of current regimen at the time of NP testing (see Table 1). In a sensitivity analysis performed only on patients at the first NP test, the association between higher CPE and poor NP tasks and enhanced NCI risk was only marginally confirmed (Beta=−0,05; [−0,12–0,02]; p=0,19; OR 1,13 [0,95–1,34]; p=0.17). Older age, longer time from HIV diagnosis, current CD4 count <350 cell/mm3 and lower education level were all associated to an increased risk of NCI.

Conclusions

In our analysis, higher CPE rank is associated to poorly performing at NP tasking. Even if selection bias could not be excluded due to retrospective cross‐sectional design, these results fitted with the direct correlation between high CPE and HIV dementia recently recorded in a large observational database. We think that CPE use to guide ART in patients neurocognitively impaired should be revised.
APRI and FIB‐4 scores are not associated with neurocognitive impairment in HIV‐infected persons
Authors: Libertone Raffaella , Balestra Pietro , Lorenzini Patrizia , Pinnetti Carmela , Ricottini Martina , Menichetti Samanta , Maddalena Plazzi Maria , Giannetti Alberto , Tozzi Valerio , Antinori Andrea , Ammassari Adriana
Published: November 2014

Introduction

Chronic liver disease leads to neurocognitive impairment (NCI) and more advanced liver fibrosis is associated with greater deficits. Further, cognitive performances do not differ significantly among patients affected by diverse types of chronic liver diseases. Thus, it would be useful to have a clinical tool associated with early cognitive change applicable to the HIV‐infected population with high HCV prevalence. Aim of the analysis was to assess the association between NCI and aspartate aminotransferase‐platelet ratio index (APRI) or Fibrosis‐4, which are non‐invasive scores used to assess liver fibrosis.

Materials and Methods

Single‐centre, retrospective, cross‐sectional analysis of cART‐treated HIV‐infected patients undergoing neuropsychological assessment (NPA) by a set of 14 standardized and comprehensive tests on five different domains: concentration and speed of mental processing; mental flexibility; memory, fine motor functioning; visual‐spatial and constructional abilities. NPA obtained from the same patient were included, if collected while receiving different cART. Patients were classified as having NCI, if they scored >1 SD below the normative mean in at least two tests, or below >2 SD in one test. HIV‐associated neurocognitive disorders (HAND) were classified according to Frascati's criteria, controlling for confounding comorbidities. Univariable analysis and multivariable logistic regression models were carried out.

Results

A total of 556 HIV‐infected cART‐treated patients from 2006 to 2013 were included: male 78%; IVDUs 14%; CDC stage C 31%; median CD4 nadir 200/mm3; median current CD4 501/mm3; undetectable HIV‐RNA in 368 (67%); and HCV‐positivity in 150 (29%). Frequency among score levels was for FIB‐4: min‐1.44=404 (73%), 1.45–3.25=118 (21%), 3.26‐max=28 (5%); for APRI: min‐0.5=414 (75%), 0.5–1.5=112 (20%), 1.5‐max=24 (4%). Median FIB‐4 and APRI were 0.98 and 0.27 in HIV+/HCV‐ and 1.40 and 0.50 in HIV+/HCV+ individuals, respectively. HAND was found in 176 (32%): 91 ANI, 73 MND, 12 HAD. Association of variables with NCI are shown in Table 1.

Conclusions

In this large population, HAND was not associated with commonly used non‐invasive liver fibrosis scores. As aetiology of cognitive dysfunction in HIV mono‐ and HCV co‐infected patients is multifactorial and partially unknown, our results support the hypothesis of a direct or indirect effect on cognitive function of the viruses, rather than the consequence of alterations residing outside the brain.
Low clinical relevance of risky alcohol consumption in a selected group of high adherent HIV‐infected patients attended in the United Kingdom
Authors: Gonzalez Baeza Alicia , Milinkovic Ana , Arenas‐Pinto Alejandro
Published: November 2014

Introduction

The prevalence of risky alcohol consumption, associated factors and its impact on the brain is not well established in clinically stable HIV patients.

Materials and Methods

Within the PIVOT neurocognitive sub‐study, effectively suppressed HIV‐infected adults on either standard cART or ritonavir‐boosted PI monotherapy completed the Alcohol Use Disorders Identification Test (AUDIT) designed to detect risky alcohol consumption. They also completed a brief neuropsychological assessment (NPZ 5) composed by five measures. For this cross‐sectional analysis, we calculated rates of hazardous (AUDIT=8–15) or harmful (AUDIT=16–19) consumption and likely dependence (AUDIT>20). We explored the association between risky alcohol intakes (AUDIT>8) and clinical/demographical variables, conducting logistic regressions when significant association was found (p<.05). Also, the association between cognitive performance and alcohol consumption was calculated and adjusted by potential confounders.

Results

Of the 146 included participants, the majority were male (86.3%), white (81.5%) and educated (mean years on formal education=15, SD=3.9). Average age was 47.6 years (SD=8.7), and 36.3% had risky consumption (29.5% hazardous, 6.2% harmful, 0.7% likely dependence). White ethnicity and male sex were positively associated with risky consumption (Table 1). After adjustments, white ethnicity remained significantly associated with risky consumption (1.64 [95% CI 0.34–2.95]; p=0.013). Better cognitive performance was associated with risky alcohol consumption in the univariate analysis (p<.001). After adjustment by ethnicity, sex and years of education, cognitive performance and risky alcohol consumption maintained significant association (0.45 [95% CI 0.19–0.70] p=0.001).

Conclusions

Despite the substantially high prevalence of risky alcohol consumption, it was not associated with worse adherence, immunological or quality of life measures in this cohort of effectively suppressed patients but prevalence of likely alcohol dependency was extremely low. White patients were more vulnerable to risky consumption. Moreover, positive association between cognitive performance and risky alcohol consumption remained after adjustment. In our study, the association we found between cognitive function and alcohol consumption does not reflect the effect of alcohol dependency on cognition.
Facial emotional processing deficits in long‐term HIV‐suppressed patients
Authors: Gonzalez‐Baeza Alicia , Perez‐Valero Ignacio , Carvajal‐Molina Fernando , Bayon Carmen , Montes‐Ramirez Marisa , Ignacio Bernardino Jose , Arribas Jose R
Published: November 2014

Introduction

Emotional processing is basic for social behaviour. We examine for the first time the facial emotion processing in long‐term HIV‐suppressed patients.

Materials and Methods

Cross‐sectional study comparing (ANOVA) six facial emotional processing tasks (two discrimination, two memory and two recognition) between HIV‐suppressed patients (HIV+) on effective antiretroviral therapy (>2 years) and matched (age, gender) healthy controls (HCs). Accuracy in the recognition of basic emotions (neutral, happiness, sadness, anger and fear) in each recognition task was also compared (Mann–Whitney U test) between HIV+ and HCs. In the subset of HIV+, we evaluate which factors were associated with impaired recognition of basic emotions (accuracy below 50%) by multiple logistic regression analysis. Overall performance in all six emotional tasks were separately compared between neurocognitive impaired and non‐impaired HIV+.

Results

We included 107 HIV+, mainly Caucasian (89%) male (72%) with a mean age of 47.4 years, neurocognitively non‐impaired (75.5%), and 40 HCs. Overall discrimination (p=0.38), memory (p=0.65) and recognition tasks (p=0.29) were similar in both groups. However, HIV+ had lower sadness recognition in both recognition tasks and lower sadness, anger and fear recognition in the facial affect selection task (Figure 1). Only estimated pre‐morbid functioning (WAIS‐III‐R vocabulary subtest score) was significantly associated with sadness (1.99 [95% CI 1.18–3.58]; p=0.01) and anger recognition deficits (2.06 [95% CI 1.14–3.45]; p=0.015) in the facial affect selection task. In HIV+ individuals, neurocognitive impairment was associated with worse memory task results (p<0.01, d=0.88; p<0.01, d=1.48).

Conclusions

We did not find difference in the overall emotion processing between HIV+ and HIV‐ individuals. However, we found particular recognition deficits in the entire HIV+ sample. Estimated pre‐morbid functioning was associated with sadness and anger recognition deficits in the facial affect selection task. Neurocognitive impaired HIV+ had additional memory deficits. These recognition deficits might conduct to social difficulties.
Co‐infections and co‐morbidities among injecting drug users versus sexually infected patients in Bucharest
Authors: Manea Eliza , Jipa Raluca , Niculescu Iulia , Benea Serban , Benea Otilia , Arama Victoria , Hristea Adriana
Published: November 2014

Introduction

After the 2008 introduction of new psychoactive substances (NPS) in Romania, the number of newly diagnosed HIV infections showed significant increase among injecting drug users (IDUs). Our objective was to analyze the differences between co‐infections related to the HIV infection, based on the way of transmission (IDUs versus sexually infected).

Materials and Methods

A retrospective transversal study was carried out, analyzing 245 adult HIV‐positive patients, diagnosed between January 2013 and December 2013 in our hospital. We collected socio‐demographic, epidemiological and laboratory data at the diagnosis and analyzed them using SPSS version 20.

Results

Most patients (71%, 174/245) were men and the median age was 32 years (IQR: 26–38). 91 patients (37%) were former/active IDUs (most of them injecting both opioids and NPS), while 154 patients (63%) were sexually infected, with 84% being heterosexuals and 16% men having sex with men (MSM). The median CD4 count, at the moment of diagnosis, was 294 cells/mm3 (IQR: 119–483).

Other co‐infections at diagnosis were toxoplasmosis (four patients), cryptococcosis (two patients) and cytomegalovirus reactivations (three patients) without significant association between the two groups.

Conclusion

Heterosexual transmission was the most common way of HIV transmission in 2013 in contrast with EU/CEE, where MSM accounted for the majority of cases of HIV epidemics in 2012 [1]. Sexually transmitted HIV infection was associated with late presentation, stage C and syphilis. We noted a high percentage of IDU transmission, which was associated with stage A and hepatitis C infection.
Difference in factors associated with low‐level viraemia and virological failure: results from the Austrian HIV Cohort Study
Authors: Leierer Gisela , Rieger Armin , Steuer Andrea , Sarcletti Mario , Geit Maria , Haas Bernhard , Taylor Ninon , Kanatschnig Manfred , Rappold Michaela , Ledergerber Bruno , Zangerle Robert
Published: November 2014

Introduction

For some patients, it remains a challenge to achieve complete virological suppression which is the goal of antiretroviral therapy (ART). Identifying factors associated with low‐level viraemia (LLV) and virological failure (VF) under ART might help to optimize management of these patients.

Materials and Methods

We investigated patients from the Austrian HIV Cohort Study receiving unmodified ART for >6 months with two nucleoside reverse‐transcriptase inhibitors (NRTIs) with either a non‐nucleoside reverse‐transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) or an integrase inhibitor (INSTI) between 1 July 2012 and 1 July 2013 with at least one viral load (VL) measurement below the limit of detection (BLD) or below level of quantification (BLQ) in their treatment history. VF was defined as HIV‐RNA levels ≥200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLD and BLQ were identified by using logistic regression models.

Results

Of the 2,276 patients analyzed, 1,972 (86.6%) were BLD or BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher risk for LLV and VF was found in patients with ART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from a centre which uses Abbott RealTime HIV‐1 assay compared to the other centres measuring VL by the Roche Cobas AmpliPrep/Cobas TaqMan 2.0. A higher risk for LLV but not for VF was found in patients with a higher VL before ART and shorter ART duration. A higher risk for VF but not for LLV was found in patients of younger age, originating from a high prevalence country, with a lower CD4 count and in male injecting drug users.

Conclusions

This study of well‐defined patients on stable ART over a period of more than six months gives insights into the different factors associated with LLV and VF. In patients with VF, factors associated with adherence play a prominent role, whereas in patients with LLV, the biology of viral replication comes additionally into effect. Despite its observational design, it has implications for patient management and forms the basis for future outcome studies.
A retrospective observational study of low‐level viraemia and its immunological and virological significance: which outcome to expect
Authors: Silva Joana , Pereira Karen , Rijo Joao , Alberto Teresa , Cabanas Joaquim , Gomes Perpetua , Farinha Helena , Mansinho Kamal
Published: November 2014

Introduction

Low‐level viraemia (LLV) is observed in some patients with HIV‐1 infection on stable antiretroviral therapy (ART). The significance of these findings remains controversial as it conflicts with traditional optimal clinic outcome. This study aims to evaluate the effect of LLV on the establishment of virological failure (VF) and immune deterioration.

Methods

Retrospective observational study of a cohort of HIV‐1 infected patients of an Infectious Diseases Clinic, who presented an HIV‐1 viral load of 20 to 200 cp/mL, during the year 2012. Patients who were not on ART or non‐adherent in the previous 6 months were excluded. Compliance was quantified by clinical and pharmaceutical records. Adherence was defined as ≥95% compliance rate. Demographic, clinical, immunological and therapeutic data were collected from clinical records. LLV was defined as a range of 20–200 cp/mL and stratified as transient (T‐LLV): only one measurement, persistent (P‐LLV): 2 consecutive measurements with an interval ≥3 months and recurrent (R‐LLV): ≥1 T‐LLV during an 18‐month follow‐up. Statistical analysis was performed with Microsoft Office® – Excel 2012. Kolmogorov–Smirnov test, t‐test and chi‐square test were performed for a significant p value <0.05.

Results

During 2012, 2161 HIV‐1 infected patients were evaluated at our Clinic, 93% of which were on ART. LLV was documented in 378 (19%), adherence was verified in 151 (52%). The analysis of this cohort (n=151) revealed: 77 (51%) T‐LLV, 13 (8.6%) R‐LLV and 61 (40%) P‐LLV. Mean viral load was 46 cp/mL. Mean TCD4 count was 665 cells/µL with a variation of +63 cells/µL during the study period. There was no VF documented. ART regimens were switched in 16 (11%) patients. Gastrointestinal disturbance was found in 13 (9%). Analysis showed no statistical differences between the analyzed variables (CD4 variation, time of diagnosis and treatment, duration of LLV persistence (less than or more than one year), number of ART regimens, ART regimen and type of NRTI backbone) for all groups (T‐LLV, R‐LLV, P‐LLV), except for mean viral load that showed significant superiority in the T‐LLV(38 cp/mL) and R‐LLV(36 cp/mL) vs P‐LLV(58 cp/mL) (p=0.01 and p<0.01, respectively).

Conclusions

The absence of significant differences in immunological and virological outcomes in this cohort and the absence of VF in all groups, suggests a scarce impact of LLV in patient's prognosis. Prospective studies, with longer follow‐up could bring more accurate information.
Comparison of routine versus targeted HIV testing strategies: coverage and estimated missed infections in emergency room and primary care centre
Authors: Jesús Pérez Elías María , Gomez‐Ayerbe Cristina , Muriel Alfonso , Eugenia Calonge Maria , Diaz Alberto , Pérez Elías Pilar , Martinez‐Colubi Maria , Uranga Almudena , Santos Cristina , Moreno Ana , Quereda Carmen , Navas Enrique , Moreno Santiago
Published: November 2014

Introduction

Different HIV Testing Strategies (TS) and clinical care settings had not been face to face evaluated [1]. We compared coverage, Newly Diagnosed HIV Infection (NDHI) and Estimated Missing HIV Infections (MHI) in Hospital Emergency Room (HER) and Primary Care Center (PCC), in DRIVE study (Spanish acronym of HIV infection Rapid Diagnosis) and in clinical practice the year before DRIVE.

Materials and Methods

In DRIVE study, 18–60 years old, non‐HIV‐infected population visiting an HER or a PCC were proposed both a structured risk practices and clinical conditions questionnaire (RP&CC‐Q) and a rapid HIV test. This arm is the HIV Routine TS. We analyze a hypothetical arm, where risk practices were universally assessed with an RP&CC‐Q, subsequently risk‐positive patients where HIV tested, Targeted‐TS. Coverage was assessed as the ratio of tested population (TP)/attended population (AP) in HER and PCC. TP/AP ratios were also calculated in the year before, the Clinical Practice‐TS. NDHI was expressed per ‰ tests performed. MHI was estimated assuming in the non‐tested population, overall DRIVE rate of NDHI ‰ and NDHI ‰ in negative RP&CC‐Q.

Results

A total of 5329 RP&CC‐Q and rapid HIV tests were performed to 49.64% women, median age 37 (28–47) years old, mainly 74.9% Spaniards. Confirmed NDHI was 4.1‰, and in 48, 8% of RP&CC‐Q negative NDH was 0‰. HIV screening coverage was always better in PCC than in HER, and higher in DRIVE study than in clinical practice. Estimated MHI was higher in HER and in the clinical practice‐TS. Targeted‐TS coverage was lower, but resulted in similar NDHI and MHI than routine‐TS, testing half the population, see Table 1.

Conclusions

Best HIV Testing Strategy is routine‐TS in Primary Care Center. Targeted‐TS resulted in same newly HIV diagnoses and missed HIV infections than routine‐TS with half the resources employed.
Relationship between discordant response to HAART, Tregs, immune activation and low‐level viraemia
Authors: Saison Julien , Ferry Tristan , Demaret Julie , Maucort‐Boulch Delphine , Venet Fabienne , Perpoint Thomas , Ader Florence , Icard Vinca , Chidiac Christian , Monneret Guillaume
Published: November 2014

Introduction

The incomplete immune recovery upon effective long‐term highly active antiretroviral therapy (HAART) has been associated with increased morbidity and mortality in HIV infected patients [1]. Immune cellular activation, Tregs or very low‐level viraemia has been alternatively suspected, but never investigated simultaneously [2].

Materials and Methods

We performed a cross‐sectional study in 87 aviraemic patients (men=62, mean CD4+T cells=570/mm3, mean duration of HAART=12 years). Patients with at least 500 CD4+ T cells /mm3 were classified as complete immunological responders (cIR), whereas remaining patients were classified as inadequate immunological responder (iIR). Tregs were characterized based on CD4+CD25highFoxP3+phenotype using a one‐step intracellular staining. Effector Tregs and terminal effectors Tregs were respectively defined as CD4+CD25+FoxP3+CD45RA‐, and CD4+CD25+FoxP3+CD45RA‐HLADR+phenotypes as recently described [3]. Activated T cells were identified using (i) elevated HLA‐DR expression for CD4+T cells, and (ii) increased expressions of HLA‐DR, or CD38, or both (HLADR+CD38+cells) for CD8+T cells. Very low‐level viraemia was defined as detectable viraemia between 1 and 39 cp/mL. Univariate and multivariate analyses were performed to identify determinants of iIR.

Results

Thirty‐nine patients were classified as iIR, and 48 as cIR. Patients from the iIR group were significantly older (55 vs 50 years, p=0.027), and had percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs significantly higher (5.3 vs 4%, p=0.014; 9 vs 7.5%, p=0,022; 8 vs 6.3%, p=0.01 and 1.8 vs 1.3%, p=0,033 among CD4+T cells, respectively). Neither the percentage of activated CD8+T cell nor very low‐level viraemia were found to be associated with iIR. In the multivariate analysis, nadir of CD4+T cell count and percentage of Tregs were the only two parameters independently associated with iIR (OR=2.339, p=0.001, and OR=0.803, p=0.041, respectively).

Conclusions

We present here the largest study investigating simultaneously immune response to long‐term HAART, immune activation of CD4+ and CD8+ T cells, Tregs percentages and very low‐level viraemia. Our results highlight the importance of Tregs in CD4 homeostasis. This aspect should now be prospectively explored in a large cohort of patients.
Validation of an ultrasensitive digital droplet PCR assay for HIV‐2 plasma RNA quantification
Authors: Ruelle Jean , Yfantis Vasilieios , Duquenne Armelle , Goubau Patrick
Published: November 2014

Introduction

Low or undetectable plasma viral load (VL) using current qPCR assays is common for HIV‐2 patients. Digital PCR is an emerging technology enabling more precision and reproducibility than qPCR at low DNA/RNA copy numbers. Available data related to digital droplet PCR (ddPCR, Bio‐Rad) underscore issues linked to the threshold definition of positivity, coupled to the specificity of low copy results [1].

Materials and Methods

A RT‐PCR protocol was set up using the One‐Step RT‐ddPCR Kit for Probes on the QX200 platform (Bio‐Rad, Hercules, CA) in an accredited environment (ISO15189:2012 norm). Parameters tested were in line with the digital MIQE guidelines [2]. Inter‐run coefficient of variation (CV) was established using synthetic RNA controls diluted in HIV‐negative plasma. The ddPCR assay was compared to a qRT‐PCR previously used in routine (LOQ 50 cop/mL [3]) using 46 clinical samples and the NIBSC international HIV‐2 RNA standard.

Results

The optimal PCR efficiency and the best separation between positive and negative droplets were obtained with a mixture containing 0.5 mM manganese acetate, 700 nM primers and 250 nM of the 5′FAM‐probe. Using a manual threshold to define positivity, 7.74% of negative controls (n=168) were scored as positive due to one positive droplet. The presence of two positive droplets or more was not observed for negative controls. Serial dilutions of a positive control showed excellent linearity (R2=0.999) and enabled us to define a limit of quantification of two positives droplets, which corresponds to 0.14 copies/μL in the reaction mixture and to seven copies per mL of plasma. The inter‐run coefficient of variation was 3.37% at a mean value of 4,468 cop/mL, 19.59% at 416 cop/mL and 32.28% at 8 cop/mL. The NIBSC standard of 1,000 IU was quantified 1,400 copies by ddPCR and close to 5,000 copies by qPCR (delta log superior to 0.5). Among 46 clinical samples, 22 were undetectable with both qPCR and ddPCR, 12 were detected with both methods (respective means of 10,612 and 2,224 cop/mL, delta log=0.68) and 12 others were quantified by ddPCR only below 50 cop/mL (mean=16 cop/mL).

Conclusions

We validated a ddPCR HIV‐2 VL assay that is more sensitive and more reproducible than the qPCR assay used as comparator, with a limit of quantification of 7 cop/mL of plasma. A careful definition of the limit of blank allows the management of false positive droplets, but the variable user‐defined positive threshold may be an issue for compliance to the quality norms.