bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute HIV infection (AHI) in a specialized clinical setting: case‐finding, description of virological, epidemiological and clinical characteristics
Authors: Ammassari Adriana , Abbate Isabella , Orchi Nicoletta , Pinnetti Carmela , Rozera Gabriella , Libertone Raffaella , Pierro Paola , Martini Federico , Puro Vincenzo , Girardi Enrico , Antinori Andrea , Rosaria Capobianchi Maria
Published: November 2014

Introduction

Diagnosis of HIV infection during early stages is mandatory to catch up with the challenge of limiting HIV viral replication and reservoirs formation, as well as decreasing HIV transmissions by immediate cART initiation.

Objectives

Aims were to describe (a) virological characteristics of AHI identified, (b) epidemiological and clinical factors associated with being diagnosed with AHI.

Methods

Cross‐sectional, retrospective study. All individuals diagnosed with AHI according to Fiebig's staging between Jan 2013 and Mar 2014 at the INMI “L. Spallanzani” were included. Serum samples reactive to a fourth generation HIV‐1/2 assay (Architect HIV Ag/Ab Combo, Abbott) were retested with another fourth generation assay (VIDAS DUO HIV Ultra, Biomérieux) and underwent confirmation with HIV‐1 WB (New Lav I Bio‐Rad) and/or with Geenius confirmatory assay (Bio‐Rad). WHO criteria (two env products reactivity) were used to establish positivity of confirmatory assays. In case of clinically suspected AHI, HIV‐1 RNA (Real time, Abbott) and p24 assay (VIDAS HIV P24 Bio‐Rad) were also performed. Avidity test was carried out, on confirmed positive samples lacking p31 reactivity, to discriminate between recent (true Fiebig V phase) and late infections; to avoid possible misclassifications, clinical data were also used. Demographic, epidemiological, clinical and laboratory data are routinely, and anonymously recorded in the SENDIH and SIREA studies.

Results

During the study period, we observed 483 newly HIV diagnosed individuals, of whom 40 were identified as AHI (8.3%). Fiebig classification showed: 7 stage II/III, 13 stage IV, 20 stage V. Demographic, epidemiological, and clinical characteristics of patients are shown in the Table. Overall, the study population had a median S/Co ratio at fourth generation EIA (Architect) of 49.50 (IQR, 23.54–98.05): values were significantly lower in Fiebig II‐IV than in Fiebig V (38.68 [IQR, 20.08–54.84] vs 75.72 [IQR, 42.66–249.80], p=0.01). Overall, median HIV‐1 RNA was 5.44 log copies/mL (IQR, 4.29–6.18) and the value observed in Fiebig phase II‐IV was higher than that found in Fiebig stage V (6.10 [IQR, 5.49–7.00] vs 4.69 [3.71–5.44], p<0.001). Median CD4+ cell count was 596/mmc (IQR, 410–737). cART was started in 26 patients: TDF/FTC/DRV/r/RAL=18; TDF/FTC/DRV/r=2; TDF/FTC/ATV/r=2; TDF+FTC+EFV=2; TDF/FTC/RAL=1; DRV/r+RAL=1.

Conclusions

Integration of careful epidemiological investigation, partner notification, and technical advances in virological testing are key elements in AHI case‐finding. Significant differences were found between Fiebig stages II–IV and Fiebig V with regard to virological exams.
The effect of tenofovir in renal function in HIV‐positive adult patients in the Roma health service area, Lesotho, southern Africa
Authors: Mugomeri Eltony , Olivier Dedré , van den Heever‐Kriek Elmien
Published: November 2014

Introduction

The government of Lesotho introduced tenofovir disoproxil fumarate (TDF) for first‐line antiretroviral treatment (ART), as recommended by the World Health Organization (1), in 2008. The use of TDF has been associated with renal toxicity (2); furthermore, renal function outcomes following the use of TDF has not been studied at Roma Health Service Area (RHSA) in Lesotho. Lesotho is a small landlocked country surrounded by South Africa. The study used an analytical design to compare retrospective creatinine clearance (CrCl) data of 312 (64%) antiretroviral treatment naïve adults exposed to TDF and 173 (36%) unexposed patients.

Methods

Impaired renal function was defined as CrCl less than 50 mL/min calculated using the Cockcroft‐Gault equation. The Ministry of Health and Social Welfare of Lesotho approved the study on 13 January 2012. The study included adult (excluding pregnant females) HIV patients enrolled on ART between December 2006 and December 2012 at St Joseph's Mission Hospital and at Nazareth Health Centre (RHSA). Patients at Nazareth Health Centre and at St Joseph's Mission Hospital made up 80% of the circa 4 116 HIV patients on ART. Only 485 patients met the set inclusion criteria.

Results

In 56 patients (17.9%), TDF was found to be contraindicated. The use of TDF was marginally significant factor for renal toxicity (p=0.054) in univariate analysis, but was insignificant (p=0.122) in multivariate logistic analysis. Univariate (p<0.1) and multivariate logistic regression (p<0.05) were performed using STATA® 11. Female gender (p=0.016), hypertension (p=0.009), and age>60 (p=0.004) were significantly associated with CrCl<50 mL/min outcome.

Conclusions

In this study, TDF proofed to be a weak contributing factor of renal impairment. Routine baseline renal function screening should however be adopted to prevent patients with impaired renal function receiving TDF.
Molecular epidemiology of HIV‐1 strains in Antalya, Turkey
Authors: Inan Dilara , Sayan Murat
Published: November 2014

Introduction

The aim of this study was to determine the subtype distribution of HIV‐1 strains isolated from antiretroviral therapy (ART)‐naive and on treatment patients in Antalya, the city of southern Turkey.

Materials and Methods

The study included 77 of 92 newly diagnosed HIV‐1 positive patients of last two years (between February 2012 and June 2014). HIV‐1 subtypes and circulating recombinant forms (CRFs) were identified by phylogenetic analysis of reverse‐transcriptase (codon 41–238) and protease (codon 1–99) domains (~667 bp) of pol gene region in HIV‐1 strains.

Results

Subtype B (48%, 37/77) was identified as the most common HIV‐1 subtype in Antalya that similar the other Turkish patients. Non‐B subtypes were followed as CRFs (39%, 30/77). Interestingly, CRF14_BG (12.9%, 10/77) was found for the first time in Antalya in contrast to previous observations in the other reports in Turkey. Also, subtype G (6.5%, 5/77) was detected more often than HIV‐1 subtypes in circulation of Turkey.

Conclusions

These findings may be associated with specific geographic localization of Antalya that touristic movements of city. Recognized HIV‐1 subtype diversity is major challenges in the development of a globally effective HIV vaccine.
Using dried blood spots collected under field condition to determine HIV‐1 diversity and drug resistance mutations in resource limited Tanzania
Authors: Kimaro James , Shao Elichilia , Nyombi Balthazar , Kifaro Emanuel , Maruapula Dorcas , Gaseitsiwe Simani , Musonda Rosemary
Published: November 2014

Introduction

A dried blood spot (DBS) on filter paper has been used for different tests globally and has gained popularities in resource limited settings especially during HIV/AIDS epidemic. We assessed the efficiency of molecular characterization of HIV‐1 subtypes using DBS collected under field conditions in northern Tanzania.

Materials and Methods

In 2011 and 2012, 60 DBS samples were collected under field conditions from exposed and newly diagnosed HIV‐1 infected children from Kilimanjaro (n=20), Arusha (n=20), Tanga (n=10) and Manyara (n=10).

Results and discussion

Of 60 DBS analyzed at both Protease (PR) and Reverse Transcriptase (RT) regions, 45 (75%) were analyzed, including 17 (85%) from Kilimanjaro, 15 (75%) from Arusha, 8 (80%) from Tanga, and 5 (50%) from Manyara region. All 45 DBS characterized had viral load above 1000 copies/mL with mean log10 viral loads of 3.87 copies/mL (SD 0.995). The phylogenetic results indicated presence of subtype and circulating recombinant form (CRF). In which, 24 were subtype A1 (53.33%), 16 were subtype C (35.55%), 3 were subtype D (6.67%) and 2 were CRF10_CD (4.35%). All major mutations were detected in the RT region, none from protease (PR) region. The mutations detected were Y181C (n=8), K103 (n=4) and G190A (n=1), conferring resistance to non‐nucleoside reverse transcriptase inhibitors (NNRTIs), and M184V (n=1), conferring resistance to lamivudine and emtricitabine.

Conclusions

Our results indicate that DBS collected from field conditions in resource scarcity areas can be used to determine the phylogeny of the virus and drug resistance mutations in areas with diverse HIV‐1 group M subtypes.
Temporal increase in HIV‐1 non‐R5 tropism frequency among antiretroviral‐naive patients from northern Poland
Authors: Parczewski Milosz , Leszczyszyn‐Pynka Magdalena , Witak‐Jêdra Magdalena , Maciejewska Katarzyna , Urbañska Anna
Published: November 2014

Introduction

Sequencing of the third hypervariable loop allows to identify genotype‐based HIV tropism. R5‐tropic viruses associated with early stages of infection are preferentially transmitted, while non‐R5 HIV‐1 tropism has been associated with severe immunodeficiency and lower lymphocyte CD4 nadir and may reflect delayed HIV diagnosis. In this study, we investigate the changes in tropism frequency from 2007 to 2013.

Materials and Methods

Study included 194 patients with confirmed HIV infection linked to care in 2007–2013. Baseline plasma samples from treatment naive patients were used for HIV‐1 genotypic tropism assessment based on triplicate V3 loop sequencing. Non‐R5 tropism prediction thresholds were assigned using a false positive rate (FPR) of 10% and 5.75% FPR and associated with clinical and laboratory data (age, gender, date of HIV diagnosis, route of transmission, CDC clinical category at diagnosis, pretreatment HIV viral load, baseline and nadir lymphocyte CD4 counts). For statistics, chi‐square and Mann–Whitney U tests were used, time trends were examined using logistic regression (R statistical platform, v. 3.1.0) for binary variables and linear regression for continuous ones.

Results

Overall non‐R5 tropism frequency for the 5.75% FPR was 15.5% and 27.8% for 10% FPR. Frequency of the non‐R5 tropism predicted using 5.75% FPR increased significantly from 2007 (0%) to 2013 (25%) [OR: 1.44 (95% CI 1.14–1.86), p=0.003, rough slope +3.89%/year] (Figure 1a). With 10% FPR, the frequency changed from 7% (2007) to 33% (2013) [OR: 1.17 (95% CI 0.99–1.39), p=0.054, rough slope +3.0%/year] (Figure 1b). Baseline lymphocyte CD4 count and nadir, as well as pretreatment HIV‐1 viral loads were stable over time of observation (r=0.014, p=0.84; r=0.13, p=0.085; r=0.016, p=0.83 for CD4 baseline, nadir and HIV load, respectively). Frequency of AIDS at HIV diagnosis increased from 21.4% in 2007 to 38.0% in 2013, however trend over time was insignificant [OR: 1.1 (95% CI 0.95–1.31), p=0.19]. Temporal trends for HIV transmission route, gender, non‐B variant frequencies also were not significant.

Conclusions

R5 tropism predominates among the treatment naive individuals but increase in the frequency of non‐R5 tropic variants may limit clinical efficacy of the coreceptor inhibitors. Increased prevalence of non‐R5 HIV‐1 may be related to late care entry and higher number of AIDS diagnoses in the recent years.
Characteristics of late presenters in Bucharest
Authors: Elena Jipa Raluca , Manea Eliza , Benea Serban , Niculescu Iulia , Benea Otilia , Mardarescu Mariana , Andrei Cosmina , Moroti Ruxandra , Hristea Adriana
Published: November 2014

Introduction

Late presentation is associated with increased healthcare costs, rates of HIV transmission and poor outcome. In Romania, in 2012, one third of individuals with new HIV diagnosis were late presenters (LP).

Objective

The aim of the study was to evaluate the epidemiological and clinical characteristics associated with late presentation.

Methods

We retrospectively studied patients over 18 years old, notified in our institution between January 2012 and December 2013, including 499 out of 727 newly diagnosed patients in Bucharest. LP were defined as patients presenting with CD4 T‐cell count below 350 cells/mm3 or with an AIDS defining event. Patients with advanced HIV disease (AHD) were defined as persons with a CD4 T‐cell count below 200 cells/mm3. Differences between groups were analyzed using the Mann‐Whitney U test for continuous variables and the chi‐square test for dichotomous variables. Multivariable analysis was performed using binary logistic regression.

Results

Out of 499 patients included, 362 (72%) were male. The median age was 30 (IQR 26–36). A total of 302 (61%) were LP and 184 (37%) were patients with AHD. A total of 170 (34%) were asymptomatic and 114 (23%) presented with an AIDS‐defining event. The median CD4 count was 293 cells/mm3 (IQR 125–471) and the median HIV viral load was 100,191 copies/mL (IQR 34,560–272,936). Characteristics of LP compared with non‐LP are shown in Table 1. Stage C disease has been shown by multivariable analysis to be associated with LP (p<0.001, OR=11.56, 95% CI 4.94–27.03).

Conclusions

More than half of newly HIV diagnosed patients in Bucharest were LP. The proportion of LP was highest among heterosexually acquired cases. Although most our patients were young, late presentation was associated with age over 35 years. The lower proportion of LP among IVDU compared with those heterosexually infected could be explained by a higher proportion of HIV screening tests among IVDU.
The use of TDM in pregnant HIV‐positive women: a retrospective cross‐sectional review of five years practice in two large hospitals in Manchester
Authors: Whitfield Thomas , Dessain Amabel , Taylor Kelly , McQuillan Orla , Looi Evelyn , Kingston Margaret , Ajdukiewicz Katherine
Published: November 2014

Introduction

Despite plasma levels of certain HIV drugs decreasing in the third trimester of pregnancy there is no definitive evidence that therapeutic drug monitoring (TDM) improves HIV control and prevents mother‐to‐child transmission (MTCT). Indeed “one‐off” TDM measurements are thought to poorly correlate with overall drug exposure [1]. We aim to describe baseline demographic and clinical characteristics of pregnant women with HIV, and to compare their HIV control, management during pregnancy and neonatal outcomes with respect to whether TDM was performed.

Materials and Methods

Retrospective cross‐sectional case note analysis was performed on pregnant women with HIV who attended North Manchester General Hospital and Manchester Royal Infirmary from 1st January 2008 to 28th May 2013.

Results

A total of 171 pregnancies were included; 39% (n=66) had TDM. The majority of patients were of African origin (85%) and age range was 16–42 years (median 32 years). TDM was found to be associated with a history of poor adherence to therapy (TDM 23%, vs no TDM 10%, p=0.017), although baseline viral load (VL) and CD4 counts were comparable between TDM and non‐TDM groups (p=0.4756 and 0.9492, respectively). TDM was also associated with protease inhibitors (PI) (TDM 94% vs no TDM 77%, p= 0.004). Within the PI group, TDM was more strongly associated with atazanavir use than other PI's (55%, p=0.023). TDM was not associated with any other demographic variable or with either of the two hospital sites (p=0.427). TDM was associated with medication alterations during pregnancy (TDM 67% vs no TDM 13%, p=0.052), but was not associated with any difference in outcomes with similar proportions of newly detectable VL during pregnancy (TDM 12% vs no TDM 7%, p=0.220) and VL detectable at birth (TDM 14% vs no TDM 9%, p= 0.293). There were no instances of MTCT.

Conclusions

TDM was associated with PI use and a history of poor adherence at baseline. TDM was not associated with improved HIV control during pregnancy and there was no MTCT. TDM was not shown to have any additional benefit in pregnancy and its routine use is not recommended to improve HIV control or reduce MTCT.
Transmitted drug resistance in women with intrapartum HIV‐1 diagnosis: a pilot epidemiological survey in Buenos Aires, Argentina
Authors: Cecchini Diego , Zapiola Ines , Fernandez Giuliano Silvina , Martinez Marina , Rodriguez Claudia , Belen Bouzas Maria
Published: November 2014

Introduction

Surveillance of primary resistance to antiretroviral drugs is particularly important in pregnant population, in which infection by drug‐resistant HIV has not only implications for maternal treatment, but could also jeopardize the efficacy of neonatal prophylaxis. We aim to describe the prevalence of resistance associated mutations (RAMs) in pregnant women with intrapartum HIV diagnosis in a public hospital of Buenos Aires, Argentina.

Materials and Methods

Prospective pilot study (period from 2008 to October 2013). Plasma samples were tested for viral load by Versant HIV‐1 RNA 3.0 (bDNA) and sequenced using HIV‐1 TRUGENE™Genotyping Kit (Siemens). The prevalence of RAMs was analyzed according to World Health Organization (WHO) criteria.

Results

Of 231 HIV‐infected pregnant women assisted, 6% (n=14) had intrapartum diagnosis of HIV infection. 12 patients (85.7%) had previous pregnancies, 10 (71.4%) had inadequate prenatal care and 3 (23.1%) seroconverted during pregnancy. Maternal characteristics (expressed medians and ranges) were: age 25.5 (16–35) years; gestational age at birth: 39 (30–42) weeks; CD4 count: 500 (132–925) cells/µL; viral load: 9418 (1800–55299) copies/mL. No one had hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection; four (33.3%) had syphilis. Eight patients (57.1%) had vaginal delivery and six emergency C‐section (42.9%). In six cases (46.2%), membrane rupture was spontaneous; four patients (28.6%) failed to receive intrapartum zidovudine (ZDV) infusion. In 12 patients a genotypic resistance test was performed: two (16.7%) had WHO RAMs corresponding to K103N mutation in both cases, conferring high‐level resistance to nevirapine (NVP) and efavirenz. Two newborns (14.3%) were preterm. All received neonatal prophylaxis: ZDV in 1 case and combined prophylaxis (ZDV/3TC/NVP) in the remaining 13 (92.9%). All newborns were formula‐fed. Two (14.3%) had congenital syphilis, one of whom died. One newborn was HIV‐infected (positive proviral DNA at 24 hours of life, wild‐type HIV).

Conclusions

This pilot study suggests that levels of transmitted resistance in this high‐risk population of pregnant women could be moderate to high. We preliminarily observed high‐level resistance to NVP: if this finding is confirmed with a larger sample, it could potentially jeopardize the utility of this drug in the combined neonatal prophylaxis recommended in the absence of maternal antiretroviral therapy.
Targeted destruction of HIV‐positive cells
Authors: Sharma Jyoti R , Dodgen Cleo , Skepu Amanda , Meyer Mervin
Published: November 2014

Introduction

HIV/AIDS is now a global epidemic that has become the leading infectious killer of adults worldwide. Although antiretroviral (ARV) therapy has dramatically improved the quality of life and increased the life expectancy of those infected with HIV but frequency of dosing and drug toxicity as well as the development of viral resistance pose additional limitations. The rapidly expanding field of nanotechnology has vast potential to radically advance the treatment and prevention of HIV/AIDS. Nanoparticles can provide improved drug delivery, by virtue of their small size, robustness, safety, multimodality or multifunctionality.

Aims and objectives

Since HIV primarily infects CD4+ cells; we aim to use CD4 as a selectable target to deliver a pro‐apoptotic protein to HIV‐infected cells using nanoparticles as carriers. The aim of study was to develop a nanotechnology‐based death inducing delivery system for the destruction of CD4+HIV infected cells through the activation of caspase‐3.

Methodology

A modified caspase‐3 protein (Mut‐3) was engineered, which is cleavable only by HIV‐1 protease. Mut‐3 can activate apoptosis in the presence of HIV‐1 protease, consequently killing HIV‐positive cells. Mut‐3 protein was conjugated to gold nanoparticles together with a CD4‐targeting peptide. The efficacy of the gold nanoparticles was tested on CHO cells that were genetically engineered to express GFP labelled CD4 and HIV‐1 protease.

Results

Mut‐3 was expressed in bacterial cells and purified. CHO cells that stably over express CD4‐GFP and HIV‐1 protease were selected using Fluorescence Activated Cell Sorting. Dose response cell culture experiments showed that gold nanoparticles without Mut‐3 and CD4‐targeting peptide did not induce cell death in CHO cells, while gold nanoparticles that was conjugated with Mut‐3 and the CD4‐targeting peptide rapidly induced cell death in CHO cells.

Conclusions

Our results suggest that gold nanoparticles conjugated with Mut‐3 and a CD4‐targeting peptide could potentially induce apoptosis in HIV‐infected cells.
Viro‐immunological characterization of naïve patients with high cerebrospinal fluid (CSF) HIV RNA
Authors: Iannuzzi Francesca , Bai Francesca , Merlini Esther , Trunfio Mattia , Borghi Lidia , Bini Teresa , d'Arminio Monforte Antonella , Marchetti Carla Giulia
Published: November 2014

Background

HIV can spread into the central nervous system (CNS) early in the course of infection and this turns into intrathecal inflammation and neuronal damage. We aimed to investigate clinical and immunological parameters associated with elevated CSF VL in HIV‐infected ART‐naïve patients.

Materials and Methods

HIV+ ART‐naïve patients underwent a comprehensive battery of neurocognitive (NC) tests and lumbar puncture (LP) for CSF HIV‐RNA detection. Plasma HIV‐RNA and peripheral T‐cell immune‐phenotypes (CD38/CD45RA/CD45R0/CD127 on CD4/CD8) were also assessed (flow cytometry). High‐CSF HIV RNA was defined as≥10000cp/mL (H‐CSF), while CSF HIV RNA<10000cp/mL characterized low VL patients (L‐CSF). Chi‐square and Mann‐Whitney tests were used. Parameters independently associated with CSF VL were explored by multivariate regression.

Results

A total of 131 patients were retrospectively enrolled. Forty‐two patients (32%) had CSF VL >10000 cp/mL.

Table 1 shows the features of H‐ versus L‐CSF patients. Compared to L‐CSF patients, H‐CSF patients displayed lower current CD4+%, lower CD4/CD8 ratio and higher CD8%. No differences in NC tests performance were observed between groups (p=0.6). Regarding T‐cell immuno‐phenotypes, H‐CSF patients displayed a higher proportion of CD45R0+CD38+CD8+ (11 vs 7%, p=0.02) and lower expression of CD45RA+CD8+ % (16 vs 20%, p=0.007), in comparison to L‐CSF patients. In multivariate analysis CD45RA+CD8+ T‐cells % (OR 0.917, CI 95% 0.852–0.987, p=0.002) was associated with H‐CSF, even after adjustment for plasma VL, CD8 and CD4 count. Globally, in univariate CSF VL inversely correlated with CD45RA+CD8+ % (r=−0.223, p=0.0217) and CD127+CD4+ % (r= −0.204, p= 0.0225), while a positive association was found between CSF and plasma VL (r=0.303, p=0.0004) and CD8 % (r=0.211, p=0.016). In multivariate linear regression, in addition to positive association between plasma and CSF VL (β: 0.212, 95% CI 0.02–0.41, p=0.032), also CD45RA+CD8+ % were confirmed inversely associated to CSF VL (β: 0.21, 95% CI −0.5 to −0.002, p=0.036), adjusting for CD4/CD8 and CD4CD127 %.

Conclusions

We hereby describe a 32% prevalence of H‐CSF in a cohort of HIV+ ART‐naïve patients. Subjects with high‐CSF viral replication are mostly with higher systemic immune activation, in particular the percentage of naïve CD8 T‐cell is positively associated with CSF VL, irrespective of plasma VL. In HIV+ ART‐naïve patients, especially if featuring a hyperactivated T‐cell immune‐phenotype, lumbar puncture should be considered to further guide CNS‐targeted cART.
Factors associated with HPV‐DNA clearance in a cohort of HIV‐positive patients: role of cART and gender
Authors: Suardi Elisa , Bai Francesca , Comi Laura , Pandolfo Alessandro , Rovati Marco , Barco Ambra , Dalzero Serena , Cassani Barbara , Marchetti Giulia , D'Arminio Monforte Antonella
Published: November 2014

Introduction

We aimed to assess any factors associated with dysplasia regression and with HPV clearance in a cohort of HIV+ patients, with particular focus on cART and gender.

Methods

Asymptomatic HIV+ patients of the San Paolo Infectious Disease (SPID) cohort who underwent anoscopy/gynaecological evaluation were enrolled. Anal/cervical brushing were analyzed for: HPV‐PCR detection/genotyping (HR‐HPV), cytologic abnormalities (Bethesda System 2001: LSIL‐HSIL). Demographics and HIV‐related parameters were evaluated at baseline. Activated CD8+/CD38+ lymphocytes were measured (flow citometry). Patients were examined at baseline (T0) and at 12–18 months visit (T1). HPV clearance was defined as negativisation of HPV at T1; SIL regression (SIL‐R) and progression (SIL‐P) were defined as change from HSIL/LSIL to a lower‐grade/absence of dysplasia and as change from absence of HSIL/LSIL to a higher‐grade dysplasia at T1, respectively. Mann Whitney test, Chi‐square test and multivariate logistic regression were used.

Results

A total of 189 patients were examined, 60 (32%) were women. One hundred fifty patients (79%) were HPV+, 113 (75%) harboured HR‐HPV; 103 (68%) showed LSIL/HSIL at T0 (32% of women and 65% of men) (all were HPV‐positive). No differences in demographics and HIV‐related markers were found between patients with SIL‐P (33, 41%) and patients with SIL‐R (47, 59%). HPV+ patients who cleared HPV (28, 18%) were found to be more frequently female, heterosexual infected, more frequently on cART and with lower Log10 HIV‐RNA and lower levels of CD8+/CD38+ % compared with HPV persistence group (Table 1).

No differences in PI exposure were found between the two groups (p=.08). Interestingly, also when only HR‐HPV were considered, clearance was associated with exposure to cART (naïve 4%, vs cART 86%, p=.048). In multivariate analysis, heterosexuals (AOR 5.123, 95% CI 1.5–17.5 vs homosexuals) were independently associated to HPV clearance, whereas CD8+/CD38+% (AOR 0.44, 95% CI 0.65–1.01 for each % more) were predictive of HPV persistence.

Conclusions

Close follow‐up of HPV and SIL should be promoted particularly in men and in untreated individuals. We cannot exclude behavioural variables linked to risky sex and reinfection.
Improvement of endothelial function after switching previously treated HIV‐infected patients to an NRTI‐sparing bitherapy with maraviroc
Authors: Bernal Enrique , Miguel Gomez Verdú Jose , Vera Francisco , Martinez Onofre , Bravo Joaquin , Galera Carlos , Muñoz Angeles , Garcia Eva , Serrano Jose , Perez Ana , Vera Carmen , Marín Irene , Cano Alfredo
Published: November 2014

Introduction

Nucleoside reverse transcriptase inhibitor (NRTI) is associated with endothelial dysfunction and proinflammatory effects. Maraviroc (MVC) is an antagonist of CCR5 receptor. CCR5 is the receptor of RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), a mediator of chronic inflammation and endothelial function. Our aim was to evaluate the maintenance of viral suppression and improvement of endothelial function in virologically suppressed HIV‐infected patients switched to an NRTI‐sparing combined antiretroviral therapy (cART) with MVC.

Materials and Methods

This observational, non‐interventional, multicenter study was performed at the Infectious Diseases Service of Santa Lucia, Morales Meseguer, Virgen de la Arrixaca and Reina Sofía University Hospital (Murcia, Spain). The selection criteria were to be asymptomatic on a regimen with undetectable viral load (<50 HIV‐RNA copies/mL) for at least six months, no previous treatment with R5 antagonists, no evidence of previous protease inhibitor (PI) failure and available R5 tropism test. Twenty‐one HIV‐infected patients were selected after the treatment regimen was changed to Maraviroc 150 mg/once daily plus ritonavir‐boosted PI therapy. Endothelial function was prospectively evaluated through flow‐mediated dilatation (FMD) of the brachial artery at baseline and at weeks 24.

Results

We included 21 patients on treatment with PI in combination with 2 NRTI. The mean cART exposition was 133±68.9 months. Fourteen (66.6%) were males, aged 49±9 years, 15 (71.4%) smokers, 4 (19.04%) family history of coronary heart disease, 1 (5.76%) type 2 diabetes and 3 (14.28%) hypertensive, mean total cholesterol was 185.5±35 mg/dL, c‐LDL 100.2±37 mg/dL, tryglicerides 170.42±92.03 mg/dL, cHDL 52.6±15.5 mg/dL, CD4 779,5±383.28 cells/mL, nadir CD4 187,96±96 cells/mL. After 24 weeks of follow‐up of a switch to an NRTI‐sparing regimen, 95.2% of HIV‐patients on viral suppressive cART maintained viral suppression and CD4+ T cell count. This cART switch improve endothelial function in patients with lower baseline FMD levels after 24 weeks (baseline FMD −1.19±4.84 % to 24 weeks FMD 11.32±7.27%; p=0.002).

Conclusions

The results of our study show that a switch to an NRTI‐sparing bi‐therapy with MVC improves endothelial function and maintained the immune‐virologic efficacy. This regimen emphasizes the needs for further clinical studies to associate these achievements with the incidence of non‐AIDS‐defining illnesses.
Mediterranean diet: the impact on cardiovascular risk and metabolic syndrome in HIV patients, in Lisbon, Portugal
Authors: Policarpo Sara , Valadas Emilia , Rodrigues Teresa , Catarina Moreira Ana
Published: November 2014

Introduction

Metabolic syndrome (MS) is common in HIV‐infected individuals and it is associated with higher cardiovascular risk (CVR). Mediterranean diet has been associated with a better metabolic control and lower CVR.

Materials and Methods

From December 2013 to May 2014, individuals between 18 and 65 years of age, who attended the outpatient HIV Clinic at the University Hospital Santa Maria, Lisbon, were selected. Adherence to Mediterranean diet was evaluated with MedDietScore, a scale from 0 to 55 that punctuates 11 food items according to the frequency of intake. Higher scores represent higher adherence. CVR was assessed using D.A.D tool (classified as low, moderate or high risk). We excluded individuals with opportunistic disease, hospitalized in the past three months or with renal disease diagnosis. All participants gave written informed consent.

Results

In the 571 HIV patients included, 67.1% (n=383) were male, 91.6% (n=523) Caucasian, with a mean age of 46.5±8.9 years. Patients were divided in two groups: naïve (7.5%; n=43) or on antiretroviral treatment (ART) (92.5%; n=528). Mean length of HIV diagnosis was 6.7±6.5 years (naïve) and 13.3±6.1 years (ART); TCD4+ counts were above 500 cel/mm3 in 55.8% (n=24) and 67.6% (n=357) of the patients, respectively. MS was present in 33.9% (n=179) of patients in ART group and 16.3% (n=7) in naïve group. Presence of MS was associated with ART group (OR=2.7; p=0.018). MS was also associated with older age in this group (p=0.000). Overall, mean MedDietScore was 27.3±5.5. Higher score was associated with older age (r=0.319; p=0.000). Naïve patients presented a trend to higher adherence to Mediterranean diet (65.1% vs 51.7% in naïve group; p=0.090). No relation between MS and Mediterranean diet was found. Higher CVR was associated with the presence of MS in the ART group (p=0.001). In this group, individuals with moderate CVR presented higher rates of adherence to Mediterranean diet (p=0.036) when compared to low and high CVR score.

Conclusions

In this cross‐sectional study, naïve individuals presented a trend to higher adherence to Mediterranean diet. On the ART group, higher adherence to Mediterranean diet was found in individuals with moderate CVR score. We think that this might suggest that this group of patients adopt this diet only in the presence of metabolic alterations or perceived CVR. Prospective studies in HIV patients are required to determine the impact of adherence to Mediterranean diet on the reduction of CVR.
Research on demands and accessibility of health services for AIDS long‐surviving patients with AIDS‐nonrelated diseases: a survey in central China
Authors: He Na , Ye Yingfeng
Published: November 2014

Introduction

Compared with western countries, China started to provide free medicine for AIDS patients years later, which leads to the late emergence of problems on health service demands of AIDS long‐surviving patients with non‐AIDS‐related diseases. Government hasn't laid enough stress on it.

Materials and Methods

The interviews and questionnaire surveys are conducted and analyzed to get information. The interviewees include 81 AIDS long‐surviving patients in three villages and several hospitals in Shangcai, Zhumadian, and 18 AIDS‐related decision makers and health service providers.

Results

There are 79 long‐surviving patients out of 81. 58 patients have non‐AIDS‐related diseases. 21 patients get hypertension and 28 get HCV. 100% patients have been to the clinics with their real‐name IC cards for minor illness. 43 patients have been transferred to assigned hospitals at the county level. Seven have the experience utilizing health services in the municipal or provincial assigned hospitals. The problem is on accessibility. 40 patients hope to get more convenient and cheap health services. Among them, 37 say the kinds and the amount of medicine in village clinics are not adequate. Seven give up because of the expensive treatment expense. For 21 patients with hypertension, 3 buy medicine at the county‐level hospitals. The other 18 choose to buy at private pharmacy. For 28 patients with HCV, 3 are not aware they actually got HCV. Free hepatic protector medicine is provided at village clinics. Up to 11 patients have not taken any treatment for HCV.

Conclusions

Patients with hypertension go to the private pharmacy for medicine instead of higher level hospital because of lack of medicine in clinics, far distance from hospitals, cumbersome procedures in hospitals, limited dosage of prescriptions and too little discount. The situation for patients with HCV is even worse. It is predicted 70% of AIDS long‐surviving patients have HCV. The treatment is expensive and out of pocket. And free liver‐protection medicine does not work sometimes. Some patients working outside their home town do not want to reveal their health situation to get free medicine. The elderly with multiple co‐morbidities need more caring. Government should expand the scale of free medicine. Hospitals need to improve medicine plans and assist on medicine purchase. For patients, attitude decides everything.
Smoking prevalence, readiness to quit and smoking cessation in HIV+ patients in Germany and Austria
Authors: Degen Olaf , Arbter Peter , Hartmann Peter , Mayr Christoph , Buhk Thomas , Schalk Horst , Brath Helmut , Ernst Dorner Thomas
Published: November 2014

Introduction

Due to the interaction between smoking and the virus and the antiretroviral therapy, the excess health hazard due to smoking is higher in HIV+ patients than in the general population. International studies suggest a higher prevalence of smoking in HIV+ subjects compared to the general population. It was the aim of the study to assess prevalence of smoking, to analyze determinants of smoking, and to evaluate readiness to quit in HIV+ patients in Germany and Austria.

Material and Methods

Consecutive patients with positive tested HIV status, smokers and non‐smokers, who are treated in seven different HIV care centres in Austria and Germany were included. Nicotine dependence was assessed with the Fagerström Test for Nicotine Dependency (FTND), and stages of change by a standardized readiness to quit questionnaire. Self‐reported smoking status was objectified by measuring exhaled carbon monoxide levels. Smokers who wanted to quit were offered a structured smoking cessation programme, and those who did not want to quit received a 1‐minute consultation. After six months, the smoking status of all included subjects was reassessed.

Results

A total of 447 patients were included; the response rate was 92%. Prevalence of smoking was 49.4%. According to a multivariate logistic regression analysis, lower age, male sex, lower educational level, and smoking of the partner were significantly associated with the smoking status. According to the FTND, 25.3% showed a low (0–2 points), 27.6 a moderate (3–4 points) and 47.1% a high (5–10 points) dependency. Regarding stages of change, 15.4% of the smokers were in the stadium precontemplation, 48.4 in contemplation, 15.4 in preparation and 10.0 in the stadium action. 11.0% were not assignable in any stadium. Higher education level and lower grade of dependency were significantly associated with the wish to quit smoking. Six months after the baseline examination, smoking cessation visits (at least one session) was performed in 28.5% of the smokers. 13% of the smokers have quit smoking, 23% have reduced smoking and 63% did not change smoking habits positively 6 months after the first visit.

Conclusions

Prevalence rates for smoking in HIV+ subjects are higher than in the general population. Readiness to quit is, however, high, and 13% of smokers who have quit smoking after six months is a remarkable short‐term success. This observation underlines the importance and feasibility of addressing smoking habits in HIV care.
The suspected unexpected and serious adverse events of antiretroviral drugs used as HIV prophylaxis in HIV uninfected persons
Authors: Pietraszkiewicz Ewa , Firlag‐Burkacka Ewa , Horban Andrzej , Kowalska Justyna D
Published: November 2014

Introduction

With increased usage of antiretroviral drugs (ARVs) in HIV uninfected persons proper reporting on suspected unexpected serious adverse reactions (SUSARs) and continued insight into serious adverse events (SAEs) is needed for adequate information on ARVs safety in such populations.

Methods

We have evaluated medical documentation of persons receiving ARVs after non‐occupationally HIV exposure (nPEP) during five concomitant years (2009–2013). SAEs and SUSARs were evaluated by two HIV physicians and defined according to international standards. In statistical methods, Kaplan Meier survival analysis was used to estimate the probability of SAE and Cox proportional hazard models to identify independent predictors of developing SAE. Only the first SAE was included in these analyses.

Results

In total, 375 persons received nPEP. The most common reason was needle stick (43%), followed by unprotected sexual intercourse (17%), rape (10%) and first aid (10%). In 84 (22%) cases, the source patient was either known to be HIV positive or within a high risk group (active injecting drug user). In total, 170 SAEs were reported, 139 persons had only one SAE and majority developed it within first two weeks. The most frequent first SAEs were gastrointestinal disorders (22%), followed by general symptoms (9%), hypersensitivity reactions (1.6%) and CNS symptoms (1.3%). The remaining events were laboratory abnormalities of liver and kidney function, haematological disorders, other and unknown, each contributing to less than 1% of all patients. 8 (2.1%) patients have developed a SUSAR (bradycardia, vivid dreams, lymphadenopathy of the neck, increased platelet count, swelling and pain of large joints, swelling of lower limbs, peripheral oedema and loss of concentration). 22 (5.9%) persons discontinued nPEP due to adverse event and 19 (5.1%) required a paid sick leave from work. In multivariate analyzes, only age was independent predictor of developing SAE (HR 1.17; [95% CI 1.03–1.34]; p=0.02).

Conclusions

In our observation, SAEs in reaction to nPEP were frequent yet usually mild events, mostly occurring in first two weeks and rarely causing discontinuation. The only significant factor increasing the risk of SAE was age. SUSARs were rare and moderately significant. More insight into this important area is required in order to ascertain proper pharmacovigilance of ARVs usage in HIV uninfected persons.
Rilpivirine versus etravirine validity in NNRTI‐based treatment failure in Thailand
Authors: Teeranaipong Phairote , Sirivichayakul Sunee , Mekprasan Suwanna , Ruxrungtham Kiat , Putcharoen Opass
Published: November 2014

Introduction

Etravirine (ETR) and rilpivirine (RPV) are the second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTI) for treatment of HIV‐1 infection. Etravirine is recommended for patients with virologic failure from first generation NNRTI‐based regimen [1]. RPV has profile with similar properties to ETR but this agent is approved for treatment‐naïve patients [2]. In Thailand, ETR is approximately 45 times more expensive than RPV. We aimed to study the patterns of genotypic resistance and possibility of using RPV in patients with virologic failure from two common NNRTI‐based regimens: efavirenz (EFV)‐ or nevirapine (NVP)‐based regimen.

Materials and Methods

Data of clinical samples with confirmed virologic failure during 2003–2010 were reviewed. We selected the samples from patients who failed EFV‐ or NVP‐based regimen. Resistance‐associated mutations (RAMs) were determined by IAS‐USA Drug Resistance Mutations. DUET, Monogram scoring system and Stanford Genotypic Resistance Interpretation were applied to determine the susceptibility of ETR and RPV.

Results

A total of 2086 samples were analyzed. Samples from 1482 patients with virologic failure from NVP‐based regimen treatment failure (NVP group) and 604 patients with virologic failure from EFV‐based regimen treatment failure (EFV group) were included. 95% of samples were HIV‐1 CRF01_AE subtype. Approximately 80% of samples in each group had one to three NNRTI‐RAMs and 20% had four to seven NNRTI‐RAMs. 181C mutation was the most common NVP‐associated RAM (54.3% vs 14.7%, p<0.01). 103N mutation was the most common EFV‐associated RAM (56.5% vs 19.1%, p<0.01). The calculated scores from all three scoring systems were concordant. In NVP group, 165 (11.1%) and 161 (10.9%) patients were susceptible to ETR and RPV, respectively (p=0.81). In EFV group, 195 (32.2%) and 191 (31.6%) patients were susceptible to ETR and RPV, respectively (p=0.81). The proportions of viruses that remained susceptible to ETR and RPV in EFV group were significantly higher than NPV group (ETR susceptibility 32.2% vs 11.1%, p<0.01, RPV susceptibility 31.6% vs 10.9%, p<0.01), respectively.

Conclusions

RPV might be a cost saving and reasonable second line NNRTI for patients who failed EFV‐ or NVP‐containing regimens, especially in resource‐limited setting because these two agents have comparable susceptibility identified by genotyping. From our study, approximately 30% of patients who failed EFV‐based regimens had viruses that remained susceptible to RPV.
Characterization of natural polymorphic sites of the HIV‐1 integrase before the introduction of HIV‐1 integrase inhibitors in Germany
Authors: Meixenberger Karolin , Pouran Yousef Kaveh , Somogyi Sybille , Fiedler Stefan , Bartmeyer Barbara , von Kleist Max , Kücherer Claudia
Published: November 2014

Introduction

The aim of our study was to analyze the occurrence and evolution of HIV‐1 integrase polymorphisms during the HIV‐1 epidemic in Germany prior to the introduction of the first integrase inhibitor raltegravir in 2007.

Materials and Methods

Plasma samples from drug‐naïve HIV‐1 infected individuals newly diagnosed between 1986 and 2006 were used to determine PCR‐based population sequences of the HIV‐1 integrase (amino acids 1–278). The HIV‐1 subtype was determined using the REGA HIV‐1 subtyping tool. We calculated the frequency of amino acids at each position of the HIV‐1 integrase in 337 subtype B strains for the time periods 1986–1989, 1991–1994, 1995–1998, 1999–2002, and 2003–2006. Positions were defined as polymorphic if amino acid variation was >1% in any period. Logistic regression was used to identify trends in amino acid variation over time. Resistance‐associated mutations were identified according to the IAS 2013 list and the HIVdb, ANRS and GRADE algorithms.

Results

Overall, 56.8% (158/278) amino acid positions were polymorphic and 15.8% (25/158) of these positions exhibited a significant trend in amino acid variation over time. Proportionately, most polymorphic positions (63.3%, 31/49) were detected in the N‐terminal zinc finger domain of the HIV‐1 integrase. Motifs and residues essential for HIV‐1 integrase activity were little polymorphic, but within the minimal non‐specific DNA binding region I220‐D270 up to 18.1% amino acid variation was noticed, including four positions with significant amino acid variation over time (S230, D232, D256, A265). No major resistance mutations were identified, and minor resistance mutations were rarely observed without trend over time. E157Q considered by HIVdb, ANRS, and GRADE algorithms was the most frequent resistance‐associated polymorphism with an overall prevalence of 2.4%.

Conclusions

Detailed knowledge of the evolutionary variation of HIV‐1 integrase polymorphisms is important to understand the development of resistance in the presence of the drug. Our results will contribute to define the relevance of integrase polymorphisms in HIV‐strains resistant to integrase inhibitors and to improve resistance interpretation algorithms.
Use of deep sequencing data for routine analysis of HIV resistance in newly diagnosed patients
Authors: Fernández‐Caballero Jose‐Angel , Chueca Natalia , Alvarez Marta , Gonzalez Dimitri , García Federico
Published: November 2014

Introduction

Use of deep sequencing is becoming a critical tool in clinical virology, with an important impact in the HIV field for routine diagnostic purposes. Here, we present the comparison of deep and Sanger sequencing in newly diagnosed HIV patients, and the use of DeepChek v1.3 & VisibleChek for their interpretation and integration with virological and clinical data.

Patients and Methods

Plasma samples from 88 newly diagnosed HIV‐1‐infected patients were included in the study. Median age (IQR) was 37 (27–47), median CD4 count (IQR) was 387 (220–554), and 85% were males. Median Viral Load (Log, IQR) was 5.03 (4.51–5.53). Deep sequencing was obtained using a GS‐Junior (Roche). Sequences were preprocessed with the 454 AVA software; aligned reads were uploaded into the DeepChek v1.3 system (ABL SA). Sanger sequences (Trugene), were uploaded in parallel. Stanford algorithm (version 7.0) resistance interpretation to first line drugs and all the mutations (score≥5) were analyzed. For deep sequencing, 1%, 5% and 10% thresholds were chosen for resistance interpretation.

Results

Using VisibleChek for analysis, we were able to describe the detection of any mutation using Sanger in 37/88 patients, with a total number of 50 Stanford ≥5 mutations, K103N and E138A being the most prevalent (n=4). Using UDS‐1%, we found 72/88 patients with at least one mutation (total of 206 Stanford ≥5 mutations). Using Sanger data, 9/88 patients (10.22%) showed any resistance to NNRTIs, while none showed resistance to NRTIs or PIs. Using UDS‐10% increased resistance to NRTIs [3/88 (3.40%)], to NNRTIs 12/88 (13.63%), and to a lesser extent to PIs [1/88 (1.13%)]. Using UDS‐5% increased resistance to NRTIs [4/88 (4.54%)] and to NNRTIs [12/88 (13.63%)], but not to PIs. Using UDS‐1% increased resistance to all classes: NRTIs [14/88 (15.90%)], NNRTIs [26/88 (30.68%)], and PIs [6/88 (6.81].

Conclusions

DeepChek and VisibleChek allow for an easy, reliable and rapid analysis of UDS data from HIV‐1. Compared to Sanger data, UDS detected a higher number of resistance mutations. UDS with a 5 &10% threshold resulted in an increase in the number of patients with any degree of resistance mainly to NRTI, NNRTIs. Going down as low as 1% increased resistance to all classes. A correct definition of clinically relevant thresholds for the interpretation of minor variant detection for different classes of ARVs is needed.