bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of HIV‐1 subtypes in a Portuguese cohort
Authors: Rocha Pereira Nuno , Duro Raquel , Piñero Carmela , Malheiro Luís , Soares Jorge , Serrão Rosário , Sarmento António 
Published: November 2014

IntroductionDistribution of HIV‐1 subtypes is variable around the world, with the most common subtype in western Europe being subtype B. The aim our study was to describe the prevalence of different HIV‐1 subtypes in newly diagnosed patients and identify demographic and epidemiological characteristics related with different subtypes.Materials and MethodsRetrospective single‐centre study of patients newly diagnosed with HIV‐1 infection between 2006 and 2012. Epidemiological data was gathered and genotyping was performed in each patient identified. Demographic and epidemiological characteristics were compared between patients with subtype B and other subtypes. Continuous variables were summarized by mean and standard deviation whereas categorical variables were presented as proportions. Comparison of groups was performed using the Chi square, Fisher exact test and Student T test. Statistical significance was assumed when p<0.05.ResultsIn the period of the study, 624 patients newly diagnosed with HIV‐1 infection were submitted to genotypic testing but information about subtype was available only for 592 patients. General characteristics of the patients are summarized in Table 1. The distribution of the identified subtypes was the following: 286 (48.3%) patients had subtype B, 157 (26.5%) had subtype G, 54 (9.1%) had subtype C, 36 (6.1%) had subtype A, 32 (5.4%) had subtype F and 25 (4.2%) had CRF's. Patients with subtype B were more commonly male (p=0.001) and younger (p<0.0001) than those with subtypes other than B. Subtype B was more common in MSM patients, while non‐B subtypes were more common in heterosexual patients and in injecting drug users (p=0.001). CD4‐cell count, viral load and AIDS at presentation were not significantly different between subtypes. Resistance associated mutations were significantly more common in patients with non‐B subtypes (15.4% vs 9.8%; p=0.048).ConclusionsThe most commonly identified subtype was B in accordance with previous reports from other western European countries. However, in our cohort the proportion of non‐B subtypes is higher than that reported for other European countries, probably reflecting the influence of strong bonds with Portuguese speaking African countries. Knowledge about HIV subtypes distribution may help understanding transmission dynamics and can be an important tool in the design of preventive measures.
Severe birth defects in children perinatal exposed to HIV from a “real‐world” setting: Infectious Diseases National Institute, Bucharest, Romania
Authors: Maria Tudor Ana 
Published: November 2014

IntroductionThe shift in epidemic trends in recent years in Romania shows new problems in regard of HIV vertical transmission, firstly in intravenous drug user's mothers co‐infected with hepatitis viruses and with social problems, and secondly the children of young mothers with an old HIV infection and long antiretroviral therapy history.Materials and MethodsWe studied all HIV perinatal exposed children routinely followed up in the Paediatric Department of the National Institute of Infectious Diseases, since January 1st 2006 till December 31st 2012. The analyses consisted of describing the birth defects and association with certain risk factors: gender, mother's age at birth and exposure to antiretrovirals in the first trimester of pregnancy.ResultsWe analyzed 244 children born to HIV‐infected mothers. The incidence of HIV infection was 16.39%. The rate of birth defects was 39.34% (96/244 cases). The most frequent findings were cardiac malformations (47/96), followed by musculoskeletal defects (24/96), neurologic defects (20/96), urogenital malformations (13/96), digestive tract defects (3/93), metabolic disorders (2/96) and genetic disorders (2/96). We found nine cases of severe congenital anomalies: complex heart defect, total congenital aganglionic megacolon, anal imperforation, Dandy‐Walker syndrome, gangliosidosis, Niemann‐Pick syndrome, Down syndrome, true hermaphroditism and cleft palate. Two children died during first year of life due to severe malformations. 9% of cases had associated malformations. The gender rate was in favour of males in group with birth defects (58/38) and with no birth defects (82/66). The median age at birth in mothers was 22 years, similar in both groups. The highest mean age at birth was in offspring's mothers with neurologic congenital defects 25, 15 years old, but is not statistically significant (p=0.1). In the studied period the highest number of birth defects were found in 2012, 37 children, compared with less than 15 in previous years (not statistically significant, p=0.07). In our studied patients the risk of birth defects was not statistically associated with HIV transmission or with exposure to antiretrovirals before and in first trimester of pregnancy (p=0.88).ConclusionThe rate of birth defects among HIV‐exposed children was not significantly associated with antiretroviral exposure, but we identify very rare and severe congenital conditions. We have noticed also a trend to increasing number of birth defects in 2012 among studied patients compared to previous years.
Possible association between the stage of HIV disease, antiretroviral treatment and the nutrient composition of breast milk in the Mangaung area, South Africa
Authors: van den Heever Wilhelmina , de Wet Geta , Hattingh Moira 
Published: November 2014

IntroductionIn South Africa where replacement feeding may not be affordable, feasible or sustainable, HIV‐infected women are recommended to exclusively breastfeed their infants during the first six months of life. The question arises whether HIV disease progression and its metabolic impact on the mother will affect the nutrient composition of breast milk. The aim was to determine the possible association between HIV disease progression, as measured by the immunological markers, and the nutrient composition of breast milk.MethodsThe nutrient composition of breast milk of 100 HIV‐infected and 50 non‐infected volunteered (control group) lodging/day visiting mothers at Paediatric/Neonatal wards of National, Pelonomi and Universitas hospitals, Bloemfontein, were measured. The HIV‐infected group was subdivided into HIV‐naïve and HIV‐ARV treatment group. Breast milk and blood samples were obtained. Macronutrients namely lactose, proteins, fat, total solids and the energy content of the breast milk and micronutrient namely calcium and phosphate were measured. Blood and immunological parameters comprised of CD4/CD8+T cell counts, viral loads and full blood counts.ResultsProtein levels amongst the HIV‐infected group showed a significant elevation (p<0.0001) compared to the control group. The calcium levels of the HIV‐infected group were significantly lower (p=0.0081) than the control group. No statistically significant differences were recorded of the measured nutrients between mothers receiving treatment and the HIV‐naïve group. All the HIV patients were anaemic with haemoglobin, haematocrit and RDW below the normal range. The Spearman Correlation Coefficient was used to determine if HIV disease progression have an influence on the nutrient composition. For the HIV‐naïve group, a significant correlation was found between the viral load and percentage total solids in breast milk. A correlation between the CD4+T cell count, the percentage total solids and energy content of the breast milk was determined in the HIV‐ARV treatment group. No strong positive correlation could be established between the immunological markers, HIV disease progression and the nutrient composition in the breast milk.ConclusionsHIV mothers can breastfeed their babies even at a more advanced stage of HIV disease progression, but emphasis has been placed on exclusive breastfeeding.
The potential impact of new national guidance on primary prevention of cardiovascular disease in people living with HIV
Authors: Ahmed Nadia , Bradley Sarah , Pearson Patrick , Edwards Simon , Waters Laura 
Published: November 2014

IntroductionCardiovascular disease (CVD) is the leading cause of death in England and Wales. As people living with HIV (PLWH) age, proactive management of CVD risk factors is crucial. The long‐awaited draft guidelines for CVD from the National Institute of Clinical Excellence (NICE) propose lipid modification (with statins) and lifestyle modification for 40–74 year olds with >10% (previously >20%) 10‐year risk of CVD using QRISK2. We currently use Framingham so compared 3 CVD risk calculators in our cohort and analyzed the impact of a change in CVD threshold on the proportion of our patients who would need intervention.Materials and MethodsFramingham, QRISK2 and JBS3 cardiovascular risk calculators were compared in a group of randomly selected patients. Then, to analyze the impact of a change in primary prevention threshold on our cohort, we interrogated a prospectively collected database to identify all individuals who had a documented Framingham risk assessment and applied the current/proposed thresholds accordingly. We performed the same analysis for the three calculator subgroup (recalculating Framingham risk). Finally we surveyed HIV services in England & Wales regarding their choice of calculator.ResultsWe compared the 3 CVD risk calculators in 100 patients, see Table 1.In terms of eligibility for primary prevention 20.9% (916/4383) had documented Framingham risk assessment as part of routine care. Using a 20% threshold, 8.8% (81/916) would require intervention, increasing to 35.2% (322/916) with a threshold for intervention of 10%. Restricting analysis to the 100 patients to whom we applied all three calculators resulted in the following proportion requiring intervention with a 20%/10% threshold, respectively: Framingham 28%/76%, QRISK2 20%/53%, JBS3 15%/42% (four patients were excluded due to incomplete data).ConclusionsReducing the threshold for cardiovascular preventative measures to 10% vastly increases the number of patients requiring primary intervention, from two‐ to fourfold depending on risk calculator used. This may have significant implications, including cost, drug–drug interactions and patient experience, that HIV physicians and general practitioners will need to address, ideally in a coordinated and patient‐focused manner.
Association between abdominal aortic calcifications, bone mineral density and vertebral fractures in a cohort of HIV‐positive patients
Authors: Iannotti Nathalie , Gazzola Lidia , Savoldi Alessia , Suardi Elisa , Cogliandro Viola , Bai Francesca , Magenta Alberto , Peri Mauro , Bini Teresa , Marchetti Giulia , d'Arminio Monforte Antonella 
Published: November 2014

IntroductionEvidence from HIV‐negative cohorts suggests a link between osteoporosis and cardiovascular disease. We evaluated the presence and distribution of abdominal aortic calcifications (AAC) and its correlation with bone mineral density (BMD) and vertebral fractures (VF) in a cohort of HIV‐positive patients.Materials and MethodsIn this cross‐sectional study, 280 asymptomatic HIV‐positive patients from the SPID (“San Paolo” Infectious Diseases) cohort were submitted to lateral spine X‐ray and DXA. AAC was identified using the AAC‐8 score, which estimates the total length of calcification of the anterior and posterior aortic walls in front of vertebrae L1–L4. Low BMD was defined by T‐score or Z‐score <−1 at lumbar spine or femoral neck. VF were identified by morph‐metric analysis of X‐ray and were defined by the “spine deformity index” (SDI) ≥1 according to semiquantitative method by Genant. Associations between AAC, BMD and SDI were evaluated by univariate and multivariate logistic regression models. The relationship between the grade of AAC and SDI was evaluated by Spearman's correlation.ResultsAAC≥1 was present in 65 patients (23.2%); of these 15 patients showed moderate/severe calcifications (AAC>2). Low BMD was found in 163 patients (58.2%) and VF (SDI≥1) in 47/274 patients (17.1%). By univariate analysis, factors associated with AAC>=1 were: age (for additional 10 years older HR 3.81 [IC95% 2.64–5.51], p<0.0001) lower CD4 nadir (for additional 50 CD4 HR 0.89 [IC95% 0.82–0.97], p=0.01) AIDS‐diagnosis (HR 2.13 [IC95 % 1.11–4.08], p=0.02) and being on HAART (HR 2.75 [IC95% 1.28–5.90], p=0.009). In multivariate analysis, only age (OR 2.62, IC95% 1.72–3.99, p<0.0001) resulted significantly associated with AAC≥1. Patients with AAC≥1 had twofold increase in the risk of low BMD (HR 2.45 [IC95% 1.32–4.45], p=0.004) and VF (SDI>=1: HR 2.17 [IC95% 1.1–4.2], p=0.02) compared to patients without AAC. The grade of AAC was directly correlated with the grade of SDI (rho=0.16; p=0.008): AAC>2 determines a sixfold increase in the risk of VF (HR 6.44 [IC95% 2.21–18.79], p=0.0006). AAC≥1 predict VF independently from BMD, vitamin D status and bone turnover marker (Table 1).ConclusionsIn our HIV population, AAC resulted a strong predictor of both low BMD and VF, irrespective of factors involved in bone formation. The grade of AAC was directly correlated with the grade of VF.
Depression in HIV‐positive women is associated with changes in antiretroviral treatment regimens
Authors: Philippe Küpper‐Tetzel Claus , Göpel Siri , Khaykin Pavel , Wolf Timo , Stephan Christoph , Herrmann Eva , Brodt Hans‐Reinhard , Haberl Annette 
Published: November 2014

IntroductionDepression is a co‐morbidity of clinical significance in HIV‐positive patients with an estimated prevalence of more than 20%. Sex and gender‐related differences in depression are well described in HIV‐negative populations, demonstrating that more women are being affected. So far little is known about frequency and characteristics of depression in HIV‐positive men and women.Materials and MethodsPrimary objective of our prospective epidemiological study was the evaluation of the Beck score for depression in male and female patients of the Frankfurt HIV Cohort. The Beck Depression Inventory (BDI‐II) is a self‐report symptom inventory made up of 21 questions, each with 4 possible answers, correlating with a certain point value. Interpretation: score 14–19: mild depression; score 20–28: moderate depression; score ≥29: severe depression. Secondary objectives of the analysis were factors that might possibly influence the disposition for depression in HIV‐positive patients, e.g. age, antiretroviral treatment history, co‐morbidities and socioeconomic status.ResultsBetween January and October 2013, 348 patients were enrolled in the study, 161 women and 187 men of the Frankfurt HIV Cohort, who had a routine appointment at the HIV‐Center of the University Clinic Frankfurt. The mean age of all study participants was 45 years (range 22–80). The majority of patients were on antiretroviral therapy (91%) at study entrance. The median BDI‐II score in all patients was 8 (0–49); in female patients 10 (0–42), in male patients 6 (0–49), respectively (Table 1). Significant more women than men showed a score for moderate depression (p=0.006). Factors associated with a BDI‐II score ≥20 in women were older age (>45 years), living alone, unemployment and the number of prior changes in antiretroviral therapy.ConclusionsDepression in people living with HIV shows sex and gender‐related differences that might also influence antiretroviral treatment strategies. HIV specialists should be aware of these gender‐specific aspects and consider routine screening for depression especially in female patients of older age or those with multiple therapy changes in history.
HIV‐1 tat and rev upregulates osteoclast bone resorption
Authors: Chew Nicholas , Tan Eemin , Li Lei , Lim Ryan 
Published: November 2014

IntroductionDisruption in bone homeostasis with increased osteoclastic resorption may lead to osteoporosis. HIV tat has been found to increase differentiation of precursor cells into osteoclast (OC) [1]. Presence of soluble HIV proteins in virally suppressed HIV patients on ART may drive a bone resorption phenotype. We investigated the role of soluble HIV proteins (tat, gp120 Mn and Bal, rev and p55‐gag) on osteoclastogenesis and OC resorptive capacity.MethodsMouse monocyte RAW 264.7 cells were cultured in vitro and induced to differentiate into OCs with 50 ng/mL RANKL and 25 ng/mL mCSF. Medium was supplemented with 100 ng/mL of recombinant HIV tat, gp120 (Mn and Bal), rev, nef and p55‐gag, respectively, with zolendronate as negative control. Differentiated OCs were stained for TRAP and counted. OC resorption function was examined by culturing differentiated OCs (in the presence of respective HIV proteins) on dentin‐coated plates and examining the following (i) sealing zone formation, (ii) volume of resorption pits and (iii) area of resorption pits per field using confocal microscopy. Expression of OC specific genes including NFATc1 and cathepsin K was investigated by qPCR. Reactive oxygen species (ROS) production is essential in RANKL‐induced OC differentiation [2,3]; effect of these proteins on ROS production was assessed using the fluorescent H2DCFH‐DA. Mean fluorescence intensity was then measured by flow cytometry. TNFα production by OC precursors when incubated with tat and rev was measured by ELISA.ResultsTat and rev treatment was associated with increased OC formation by 70 and 26%, respectively (p<0.01), relative to control, while zolendronate significantly inhibited OC formation by 75%. Gp120 Mn and Bal, nef and p55‐gag treatment had no effect on OC differentiation. Interestingly, neither tat nor rev treatment caused significant increases in sealing zone formation but increased dentin resorption pit area by 28 and 19%, respectively, and resorption pit volume by 11 and 6%, respectively. Tat protein treatment was associated with upregulation of NFATc1 and cathepsin K mRNA expression by 20 and 15%, respectively. Incubation with tat and rev led to a dose‐dependent increase in intracellular ROS production in the monocytes and OC precursors and significant upregulation in TNFα cytokine production by the OC precursors.ConclusionsIn addition to their effect of OC differentiation, we demonstrated the effects of tat and rev on OC resorption. HIV tat and rev are both biologically active in driving a pro‐osteoclastic phenotype.
Failure of daily tenofovir to prevent HIV transmission or the establishment of a significant viral reservoir despite continued antiretroviral therapy
Authors: Davies Olubanke , Alexander Hannah , Robinson Nicola , Pace Matthew , Brady Michael , Frater John , Fox Julie 
Published: November 2014

IntroductionTruvada is licenced for HIV‐1 prevention in the USA and is available in the private sector. Tenofovir performed as well as Truvada in the PARTNERS PrEP study and is used as HIV pre‐exposure prophylaxis (PreP) in some settings. The clinical efficacy of Tenofovir for PrEP outside a clinical trial is unknown. Antiretroviral therapy (ART) at acute HIV‐1 infection (AHI) limits the size of the reservoir, optimizing the chance of maintaining viral control off therapy. As such ART at acute HIV infection is proposed to offer a functional cure in a minority of subjects. We present two cases where Tenofovir PrEP failed to prevent HIV acquisition and failed to limit viral reservoir.Materials and MethodsTwo individuals receiving tenofovir monotherapy for Hepatitis B monoinfection were diagnosed with AHI as defined by a negative HIV antibody test within three months of a positive HIV test following unsafe sex with casual male partners. In‐depth histories were taken. Viral genotypes and Tenofovir drug levels were measured from samples taken as close to HIV seroconversion as possible and subsequent samples were analyzed for proviral Total HIV‐1 DNA by qPCR.ResultsPatient A had received tenofovir for the preceding six years and always maintained an undetectable Hepatitis B viral load with no concerns about adherence. Two weeks preceding the positive HIV antibody test, he experienced mild symptoms (fever, pharyngitis) of HIV seroconversion. HIV status was confirmed by a repeat fourth generation HIV antibody test and by Western Blot and an HIV viral load was undetectable. Tenofovir trough level at HIV diagnosis was within normal limits. The regimen was intensified to Eviplera and a total HIV‐1 DNA was 1381 copies/million CD4 T cells. Patient B received four regimens for hepatitis B treatment before starting tenofovir monotherapy in 2011 and subsequently maintained an undetectable hepatitis B viral load. After three years of tenofovir monotherapy he developed a severe symptomatic seroconversion illness and tested HIV antibody positive. The baseline HIV viral load was 103,306 copies/mL. The regimen was intensified and total HIV‐1 DNA was 2746 copies/million CD4 T cells.ConclusionsFurther investigation into the efficacy of tenofovir for PrEP outside a clinical trial is required. ART at AHI does not always lead to a low viral reservoir. To explore the possibility of replication incompetent virus, viral outgrowth assays are underway.
Protease mutations emerging on darunavir in protease inhibitor‐naïve and experienced patients in the UK
Authors: El Bouzidi Kate , White Ellen , Mbisa Jean L , Phillips Andrew , Mackie Nicola , Pozniak Anton , Dunn David 
Published: November 2014

IntroductionDarunavir (DRV) is a preferred agent in treatment guidelines for ART‐naïve and experienced patients [1]. It is considered to have a high genetic barrier to resistance and 11 resistance‐associated mutations (RAMs) are recognized by IAS‐USA [2]. These have largely been identified by analyses examining the correlation between baseline genotype and virological response [3]. However, there is little information on RAMs that are directly selected by DRV, outside of short‐term clinical trials. We aimed to identify emerging mutations by comparing the genotypes of individuals before and after DRV exposure.Materials and MethodsThe UK HIV Drug Resistance Database was used to identify patients aged over 16 who had received at least 30 days of a DRV‐containing regimen. Patients were included if they had a “baseline” resistance test, prior to DRV exposure, and a “repeat” test, either on DRV or within 30 days of stopping this agent. To avoid attributing the effects of other PIs on emerging RAMs to DRV, patients were excluded if they had received another PI for greater than 90 days between the baseline genotype and the start of DRV. The baseline and repeat tests were compared to determine the nature of mutations stratified by PI history.ResultsA total of 5623 patients had DRV, of whom 306 met the inclusion criteria. A total of 228 (74.5%) were male, median age at the start of DRV was 42 years (IQR 37–47), and half had subtype B infection. The mode of transmission was homosexual contact for 50%, heterosexual for 38%, and 3% were injection drug users. The median CD4 count at the start of DRV was 257 cells/mm3 (IQR 94–453). A total of 149 patients (49%) had a history of PI use prior to DRV, and 157 (51%) were PI‐naïve. The most common previous PIs were lopinavir, atazanavir, and saquinavir. Baseline DRV RAMs were present in 1 (0.6%) PI‐naïve and 20 (13.4%) PI‐experienced patients. Mutations emerged under DRV pressure in a further 3 (1.9%) PI‐naïve patients, and in 7 (4.7%) PI‐experienced patients, 5 of whom had other DRV RAMs present at baseline (Table 1). The median time from the start of DRV to the repeat test was 196 days for PI‐naïve patients and 296 days for PI‐experienced.ConclusionsPI‐experienced patients had a greater prevalence of DRV RAMs at baseline than PI‐naïve individuals, probably due to the fact that some DRV RAMs can be selected by other PIs. This group also accumulated more RAMs during DRV exposure, possibly because previous PIs had caused minority variants which then emerged on DRV therapy. Overall, only 10 patients accumulated 16 RAMs, which supports the perception that DRV has a high genetic barrier to resistance. Repeat genotyping in the case of virological failure on DRV may still be warranted to detect emerging resistance and guide management decisions.