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Find video protocols related to scientific articles indexed in Pubmed.
An Immunochip based interrogation of scleroderma susceptibility variants identifies a novel association at DNASE1L3.
Arthritis Res. Ther.
PUBLISHED: 10-21-2014
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IntroductionThe aim of the study was to interrogate the genetic architecture and autoimmune pleiotropy of scleroderma susceptibility in the Australian population.MethodsWe genotyped individuals from a well-characterized cohort of Australian scleroderma patients with the Immunochip, a custom array enriched for single nucleotide polymorphisms (SNPs) at immune loci. Controls were taken from the 1958 British Birth Cohort. After data cleaning and adjusting for population stratification the final dataset consisted of 486 cases, 4,458 controls and 146,525 SNPs. Association analyses were conducted using logistic regression in PLINK. A replication study was performed using 833 cases and 1938 controls.ResultsA total of 8 loci with suggestive association (P <10-4.5) were identified, of which 5 showed significant association in the replication cohort (HLA-DRB1, DNASE1L3, STAT4, TNP03-IRF5 and VCAM1). The most notable findings were at the DNASE1L3 locus, previously associated with systemic lupus erythematosus, and VCAM1, a locus not previously associated with human disease. This study identified a likely functional variant influencing scleroderma susceptibility at the DNASE1L3 locus; a missense polymorphism rs35677470 in DNASE1L3, with an odds ratio of 2.35 (P¿=¿2.3¿×¿10¿10) in anti-centromere antibody (ACA) positive cases.ConclusionsThis pilot study has confirmed previously reported scleroderma associations, revealed further genetic overlap between scleroderma and systemic lupus erythematosus, and identified a putative novel scleroderma susceptibility locus.
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Bibliometric analysis on Australian rural health publications from 2006 to 2012.
Aust J Rural Health
PUBLISHED: 06-16-2014
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To review Australian rural health (ARH) publications in PubMed from 2006 to 2012 and address ARH issues raised by the 2013 Health and Medical Research report.
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Potential role of the lectin pathway of complement in the pathogenesis and disease manifestations of systemic sclerosis: a case¿control and cohort study.
Arthritis Res. Ther.
PUBLISHED: 05-25-2014
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IntroductionRepetitive episodes of ischemia and reperfusion (I/R) are a cardinal feature of the pathogenesis of systemic sclerosis (SSc), which precedes tissue fibrosis. The complement system is a key mediator of tissue damage after I/R, primarily by activation of the lectin pathway. This study investigated whether serum levels and polymorphisms of mannose-binding lectin (MBL) and ficolin-2 (FCN2), two pattern recognition receptors of the lectin pathway, are associated with the predisposition to, and clinical features of SSc.MethodsA case¿control study was undertaken involving 90 patients with SSc from a single SSc outpatient clinic and 90 age- and sex-matched blood donors. MBL and FCN2 levels and polymorphisms were measured in both groups, and in cases correlated with clinical data.ResultsMBL levels and genotypes were equally distributed in cases and controls while there were some significant differences in FCN2 polymorphisms. Median MBL levels were higher in SSc cases with diffuse disease compared with controls (2.6 versus 1.0 ¿g/ml, P <0.001).In some cases, higher MBL levels were associated with the presence of clinical findings associated with vascular dysfunction and local tissue damage (digital ulcers, calcinosis and pitting). Moreover, MBL levels were associated with fibrotic disease manifestations as evidenced by the presence of diffuse disease (median 2.6 versus 0.8 ¿g/ml, P =0.002), the modified Rodnan skin score (r =0.39, P <0.001), and interstitial lung disease as measured by forced vital capacity (r¿=¿¿0.33, P =0.001). Importantly, MBL levels also correlated with the SSc Health Assessment Questionnaire scores (r =0.33, P =0.002). The results for FCN2 levels were less striking. Phenotypic MBL results were largely confirmed by analysis of MBL polymorphisms. MBL levels were not associated with the presence of autoantibodies or hypocomplementaemia.ConclusionsOverall, predisposition to SSc was not influenced by the lectin pathway of complement in our matched case¿control study. However, our preliminary data suggest that MBL, and to a lesser extent FCN2 may modulate disease manifestations of SSc, particularly in diffuse cutaneous disease.
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The Center for HIV/AIDS Vaccine Immunology (CHAVI) multi-site quality assurance program for cryopreserved human peripheral blood mononuclear cells.
J. Immunol. Methods
PUBLISHED: 05-23-2014
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The Center for HIV/AIDS Vaccine Immunology (CHAVI) consortium was established to determine the host and virus factors associated with HIV transmission, infection and containment of virus replication, with the goal of advancing the development of an HIV protective vaccine. Studies to meet this goal required the use of cryopreserved Peripheral Blood Mononuclear Cell (PBMC) specimens, and therefore it was imperative that a quality assurance (QA) oversight program be developed to monitor PBMC samples obtained from study participants at multiple international sites. Nine site-affiliated laboratories in Africa and the USA collected and processed PBMCs, and cryopreserved PBMC were shipped to CHAVI repositories in Africa and the USA for long-term storage. A three-stage program was designed, based on Good Clinical Laboratory Practices (GCLP), to monitor PBMC integrity at each step of this process. The first stage evaluated the integrity of fresh PBMCs for initial viability, overall yield, and processing time at the site-affiliated laboratories (Stage 1); for the second stage, the repositories determined post-thaw viability and cell recovery of cryopreserved PBMC, received from the site-affiliated laboratories (Stage 2); the third stage assessed the long-term specimen storage at each repository (Stage 3). Overall, the CHAVI PBMC QA oversight program results highlight the relative importance of each of these stages to the ultimate goal of preserving specimen integrity from peripheral blood collection to long-term repository storage.
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Feasibility of HIV point-of-care tests for resource-limited settings: challenges and solutions.
BMC Med
PUBLISHED: 05-19-2014
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Improved access to anti-retroviral therapy increases the need for affordable monitoring using assays such as CD4 and/or viral load in resource-limited settings. Barriers to accessing treatment, high rates of loss to initiation and poor retention in care are prompting the need to find alternatives to conventional centralized laboratory testing in certain countries. Strong advocacy has led to a rapidly expanding repertoire of point-of-care tests for HIV. point-of-care testing is not without its challenges: poor regulatory control, lack of guidelines, absence of quality monitoring and lack of industry standards for connectivity, to name a few. The management of HIV increasingly requires a multidisciplinary testing approach involving hematology, chemistry, and tests associated with the management of non-communicable diseases, thus added expertise is needed. This is further complicated by additional human resource requirements and the need for continuous training, a sustainable supply chain, and reimbursement strategies. It is clear that to ensure appropriate national implementation either in a tiered laboratory model or a total decentralized model, clear country-specific assessments need to be conducted.
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Three unique presentations of atraumatic spinal cord infarction in the pediatric emergency department.
Pediatr Emerg Care
PUBLISHED: 05-03-2014
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Nontraumatic spinal cord infarction is especially rare in children. Although diagnosis is easily made with magnetic resonance imaging, the typical presenting signs and symptoms and etiology remain elusive. Evidence-based treatment courses are not available. We assess a series of 3 unique patients with nontraumatic spinal cord infarction who presented to our emergency department over the course of 2 years. We consider their presentation, etiology, and treatment course to provide other emergency department physicians with the ability to better identify and evaluate these patients. We also note the need for further research on nontraumatic spinal cord infarction because these patients' outcomes can be quite devastating.
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Xpert MTB/RIF as a measure of sputum bacillary burden. Variation by HIV status and immunosuppression.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 05-03-2014
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Xpert MTB/RIF cycle threshold values are a measure of sputum mycobacterial burden. Data on the impact of HIV infection and immunosuppression on this measure are limited.
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Drug susceptibility and resistance mutations after first-line failure in resource limited settings.
Clin. Infect. Dis.
PUBLISHED: 05-01-2014
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The development of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been associated with baseline human immunodeficiency virus (HIV)-1 RNA level (VL), CD4 cell counts (CD4), subtype, and treatment failure duration. This study describes drug resistance and levels of susceptibility after first-line virologic failure in individuals from Thailand, South Africa, India, Malawi, Tanzania.
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Multicenter feasibility study to assess external quality assessment panels for Xpert MTB/RIF assay in South Africa.
J. Clin. Microbiol.
PUBLISHED: 04-30-2014
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External quality assessment (EQA) for the Xpert MTB/RIF assay is part of the quality system required for clinical and laboratory practice. Five newly developed EQA panels that use different matrices, including a lyophilized sample (Vircell, Granada, Spain), a dried tube specimen (CDC), liquid (Maine Molecular Quality Control, Inc. [MMQCI], Scarborough, ME), artificial sputum (Global Laboratory Initiative [GLI]), and a dried culture spot (National Health Laboratory Services [NHLS]), were evaluated at 11 GeneXpert testing sites in South Africa. The panels comprised Mycobacterium tuberculosis complex (MTBC)-negative, MTBC-positive (including rifampin [RIF] susceptible and RIF resistant), and nontuberculosis mycobacterial material that was inactivated and safe for transportation. Twelve qualitative and quantitative variables were scored as acceptable (1) or unacceptable (0); the overall panel performance score for the Vircell, CDC, GLI, and NHLS panels was 9 of 12, while the MMQCI panel scored 6 of 12 (owing to the need for cold chain maintenance). All panels showed good compatibility with Xpert MTB/RIF testing, and none showed PCR inhibition. The use of a liquid or dry matrix did not appear to be a distinguishing criterion, as both matrices had reduced scores on insufficient volumes, a need for extra consumables, and the ability to transfer to the Xpert MTB/RIF cartridge. EQA is an important component of the quality system required for diagnostic testing programs, but it must be complemented by routine monitoring of performance indicators and instrument verification. This study aims to introduce EQA concepts for Xpert MTB/RIF testing and evaluates five potential EQA panels.
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Time to reduce CD4+ monitoring for the management of antiretroviral therapy in HIV-infected individuals.
S. Afr. Med. J.
PUBLISHED: 04-07-2014
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Access to antiretroviral therapy (ART) is expanding at a rapid rate in resource-limited settings, with ambitious goals such as having 90% of infected individuals on ART by 2020. With the expansion of ART, there will be the need to expand assays for both HIV diagnosis and monitoring. To achieve these goals, clinical and diagnostic algorithms need to undergo constant review to ensure that they remain relevant and have the desired impact. While all assays used in HIV care need to be considered, this opinion focuses on the changes that could be made to CD4+ testing algorithms, resulting in reduced use allowing funds to be diverted to the current gold standard assay for measuring treatment success, the HIV viral load. 
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Diagnostic accuracy of Xpert MTB/RIF for extrapulmonary tuberculosis specimens: establishing a laboratory testing algorithm for South Africa.
J. Clin. Microbiol.
PUBLISHED: 03-12-2014
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South Africa implemented Xpert MTB/RIF as the initial diagnostic test for pulmonary tuberculosis (TB). Xpert MTB/RIF's accuracy for diagnosing extrapulmonary tuberculosis (EPTB) was investigated. EPTB specimens (n = 7,916) from hospitalized patients received over a 6-month period at a high-throughput TB referral laboratory in Johannesburg were investigated. Large-volume specimens were centrifuged, tissue biopsy specimens homogenized, and all specimens checked for growth of contaminating bacteria on blood agar. Contaminated samples received NALC-NaOH (N-acetyl-l-cysteine-sodium hydroxide) decontamination prior to liquid culture. Residual specimens (volumes > 1 ml) after inoculation of culture (n = 1,175) were tested using the Xpert MTB/RIF sputum protocol. Using culture as the reference, Xpert MTB/RIF's overall sensitivity was 59% (95% confidence interval [95% CI], 53% to 65%) and specificity was 92% (CI, 90% to 94%), with the highest sensitivities of 91% (95% CI, 78% to 97%) for pus, 80% (95% CI, 56% to 94%) for lymph node aspirates, and 51% (95% CI, 44% to 58%) for fluids (ascitic, 59%; pleural, 47%). A difference in sensitivities was noticed between specimens classified as having a thick (87% [95% CI, 76% to 94%]) versus clear (watery) (48% [95% CI, 36% to 61%]) appearance. This was unchanged with traces of blood (52% [95% CI, 44% to 60%]) or precentrifugation (57% [95% CI, 28% to 82%]) among clear specimens. Xpert MTB/RIF generated an additional 124 specimen results that were contaminated by Mycobacterial Growth Indicator Tubes (MGIT; 10.5%) and diagnosed rifampin (RIF) resistance earlier (9.6% [25/260]). Xpert MTB/RIF's performance on EPTB specimens provides very promising results and should be considered for incorporation into national TB guidelines. Xpert MTB/RIF is less affected by contaminating bacteria and reduces laboratory labor and diagnostic delay compared to traditional methods.
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High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen.
PLoS ONE
PUBLISHED: 01-01-2014
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The knowledge-base of emerging drug resistance profiles in children exposed to abacavir-based antiretroviral regimens in South Africa is very limited. This study investigated the suitability of didanosine-based 2nd-line regimens for children in the context of antiretroviral drug resistance patterns emerging after 1st-line virologic failure.
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Systematic review of the use of dried blood spots for monitoring HIV viral load and for early infant diagnosis.
PLoS ONE
PUBLISHED: 01-01-2014
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Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID.
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Identification of a 251 gene expression signature that can accurately detect M. tuberculosis in patients with and without HIV co-infection.
PLoS ONE
PUBLISHED: 01-01-2014
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Co-infection with tuberculosis (TB) is the leading cause of death in HIV-infected individuals. However, diagnosis of TB, especially in the presence of an HIV co-infection, can be limiting due to the high inaccuracy associated with the use of conventional diagnostic methods. Here we report a gene signature that can identify a tuberculosis infection in patients co-infected with HIV as well as in the absence of HIV.
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Systematic review of the performance of HIV viral load technologies on plasma samples.
PLoS ONE
PUBLISHED: 01-01-2014
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Viral load (VL) monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring.
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Viral Tropism and Antiretroviral Drug Resistance in HIV-1 Subtype C-Infected Patients Failing Highly Active Antiretroviral Therapy in Johannesburg, South Africa.
AIDS Res. Hum. Retroviruses
PUBLISHED: 12-13-2013
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Abstract Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C-infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug-naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HIV-1 subtype C with at least one antiretroviral drug resistance mutation. Viral tropism prediction in individuals failing HAART revealed similar proportions (29%) of X4-utilizing viruses compared to antiretroviral drug-naive patients (30%). Findings are in contrast to reports from Durban in which 60% of HAART-failing subjects harbored X4/dual/mixed-tropic viruses. Despite differences in proportions of X4-tropism within South Africa, the high proportion of thymidine analogue mutations (TAMs) and CXCR4-utilizing HIV-1 highlights the need for intensified monitoring of HAART patients and the predicament of diminishing drug options, including CCR5 antagonists, for patients failing therapy.
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HIV-HBV coinfection in Southern Africa and the effect of lamivudine- versus tenofovir-containing cART on HBV outcomes.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 07-30-2013
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This study assessed HIV-hepatitis B virus (HBV) coinfection in southern Africa in terms of prevalence, viral characteristics, occult HBV, and the effect of lamivudine- versus tenofovir-containing first-line combination antiretroviral treatment (cART) on HBV-related outcomes.
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Using Xpert MTB/RIF.
Curr Respir Med Rev
PUBLISHED: 07-12-2013
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Xpert MTB/RIF is an automated real-time polymerase chain reaction test for simultaneous detection of tuberculosis and rifampicin resistance. Xpert MTB/RIF has demonstrated excellent accuracy in clinical evaluation studies, but has reduced sensitivity for detection of smear-negative tuberculosis. Since sample processing and detection are largely automated, Xpert MTB/RIF is potentially suitable for implementation in resource-limited settings. There are, however, a number of practical constraints to the use of Xpert at the point-of-care. Xpert remains a relatively costly test, and clear demonstration of cost-effectiveness will be needed to support efforts to scale up testing in high burden countries.
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Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine.
J. Infect. Dis.
PUBLISHED: 05-21-2013
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The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure.
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Development and evaluation of an affordable real-time qualitative assay for determining HIV-1 virological failure in plasma and dried blood spots.
J. Clin. Microbiol.
PUBLISHED: 04-17-2013
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Virological failure (VF) has been identified as the earliest, most predictive determinant of HIV-1 antiretroviral treatment (ART) failure. Due to the high cost and complexity of virological monitoring, VF assays are rarely performed in resource-limited settings (RLS). Rather, ART failure is determined by clinical monitoring and to a large extent immunological monitoring. This paper describes the development and evaluation of a low-cost, dried blood spot (DBS)-compatible qualitative assay to determine VF, in accordance with current WHO guideline recommendations for therapy switching in RLS. The assay described here is an internally controlled qualitative real-time PCR targeting the conserved long terminal repeat domain of HIV-1. This assay was applied to HIV-1 subtypes A to H and further evaluated on HIV-1 clinical plasma samples from South Africa (n = 191) and Tanzania (n = 42). Field evaluation was performed in Uganda using local clinical plasma samples (n = 176). Furthermore, assay performance was evaluated for DBS. This assay is able to identify VF for all major HIV-1 group M subtypes with equal specificity and has a lower detection limit of 1.00E+03 copies/ml for plasma samples and 5.00E+03 copies/ml for DBS. Comparative testing yielded accurate VF determination for therapy switching in 89% to 96% of samples compared to gold standards. The assay is robust and flexible, allowing for "open platform" applications and producing results comparable to those of commercial assays. Assay design enables application in laboratories that can accommodate real-time PCR equipment, allowing decentralization of testing to some extent. Compatibility with DBS extends access of sampling and thus access to this test to remote settings.
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The inclusion of N-terminal pro-brain natriuretic peptide in a sensitive screening strategy for systemic sclerosis-related pulmonary arterial hypertension: a cohort study.
Arthritis Res. Ther.
PUBLISHED: 04-15-2013
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Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accuracy of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with pulmonary function tests (PFT) (proposed algorithm) in a screening algorithm for SSc-PAH.
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A pragmatic approach to HIV-1 drug resistance determination in resource-limited settings by use of a novel genotyping assay targeting the reverse transcriptase-encoding region only.
J. Clin. Microbiol.
PUBLISHED: 03-27-2013
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In resource-limited settings (RLS), reverse transcriptase (RT) inhibitors form the backbone of first-line treatment regimens. We have developed a simplified HIV-1 drug resistance genotyping assay targeting the region of RT harboring all major RT inhibitor resistance mutation positions, thus providing all relevant susceptibility data for first-line failures, coupled with minimal cost and labor. The assay comprises a one-step RT-PCR amplification reaction, followed by sequencing using one forward and one reverse primer, generating double-stranded coverage of RT amino acids (aa) 41 to 238. The assay was optimized for all major HIV-1 group M subtypes in plasma and dried blood spot (DBS) samples using a panel of reference viruses for HIV-1 subtypes A to D, F to H, and circulating recombinant form 01_AE (CRF01_AE) and applied to 212 clinical plasma samples and 25 DBS samples from HIV-1-infected individuals from Africa and Europe. The assay was subsequently transferred to Uganda and applied locally on clinical plasma samples. All major HIV-1 subtypes could be detected with an analytical sensitivity of 5.00E+3 RNA copies/ml for plasma and DBS. Application of the assay on 212 clinical samples from African subjects comprising subtypes A to D, F to H (rare), CRF01_AE, and CRF02_AG at a viral load (VL) range of 6.71E+2 to 1.00E+7 (median, 1.48E+5) RNA copies/ml was 94.8% (n = 201) successful. Application on clinical samples in Uganda demonstrated a comparable success rate. Genotyping of clinical DBS samples, all subtype C with a VL range of 1.02E+3 to 4.49E+5 (median, 1.42E+4) RNA copies/ml, was 84.0% successful. The described assay greatly reduces hands-on time and the costs required for genotyping and is ideal for use in RLS, as demonstrated in a reference laboratory in Uganda and its successful application on DBS samples.
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Patient perceptions of barriers to the early diagnosis of lung cancer and advice for health service improvement.
Fam Pract
PUBLISHED: 02-01-2013
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Patient and systematic factors within primary and secondary care contribute to delay in timely diagnosis of lung cancer. This qualitative study aimed to explore New Zealand service users experiences of the pathway to lung cancer diagnosis, identify factors contributing to delay and provide advice for service improvement.
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Feasibility of Performing Multiple Point of Care Testing for HIV Anti-Retroviral Treatment Initiation and Monitoring from Multiple or Single Fingersticks.
PLoS ONE
PUBLISHED: 01-01-2013
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Point of Care testing (POCT) provides on-site, rapid, accessible results. With current South African anti-retroviral treatment guidelines, up to 4 fingersticks /patient/clinic visit could be required if utilizing POC. We determined the feasibility and accuracy of a nurse performing multiple POCT on multiple fingersticks followed by simplification of the process by performance of multiple POC on a single fingerstick.
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Low Prevalence of Liver Disease but Regional Differences in HBV Treatment Characteristics Mark HIV/HBV Co-Infection in a South African HIV Clinical Trial.
PLoS ONE
PUBLISHED: 01-01-2013
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Hepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA Safeguard the household study in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation.
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Time to treatment and patient outcomes among TB suspects screened by a single point-of-care xpert MTB/RIF at a primary care clinic in Johannesburg, South Africa.
PLoS ONE
PUBLISHED: 01-01-2013
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In December 2010, the World Health Organization recommended a single Xpert MTB/RIF assay as the initial diagnostic in people suspected of HIV-associated or drug resistant tuberculosis. Few data are available on the impact of this recommendation on patient outcomes. We describe the diagnostic follow-up, clinical characteristics and outcomes of a cohort of tuberculosis suspects screened using a single point-of-care Xpert.
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Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study.
Lancet Infect Dis
PUBLISHED: 10-27-2011
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The effect of pretreatment HIV-1 drug resistance on the response to first-line combination antiretroviral therapy (ART) in sub-Saharan Africa has not been assessed. We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large prospective cohort.
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Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort.
Arthritis Res. Ther.
PUBLISHED: 10-02-2011
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The prevalence of antibodies to RNA polymerase III (anti-RNAP) differs among systemic sclerosis (SSc) cohorts worldwide. Previously reported associations of anti-RNAP include diffuse cutaneous disease, tendon friction rubs and renal crisis, with recent reports suggesting a close temporal association between malignancy and SSc disease onset among patients with anti-RNAP.
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Natural killer cell activation distinguishes Mycobacterium tuberculosis-mediated immune reconstitution syndrome from chronic HIV and HIV/MTB coinfection.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-10-2011
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With increased access to antiretroviral treatment (ART), immune reconstitution inflammatory syndrome (IRIS) in Mycobacterium tuberculosis (MTB)-infected populations remains a clinical challenge. We studied a cross-sectional cohort of HIV-infected subjects in Johannesburg (South Africa) to help define the immune correlates that best distinguish IRIS from ongoing MTB cases.
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Accumulation of HIV drug resistance mutations in patients failing first-line antiretroviral treatment in South Africa.
AIDS Res. Hum. Retroviruses
PUBLISHED: 08-05-2011
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Patients failing antiretroviral treatment for extended periods of time are at risk of accumulating HIV drug resistance mutations (DRMs), which negatively influences second-line treatment. This retrospective study assessed the rate of DRM accumulation among South African patients with continued virological failure. Serial genotypic resistance testing was performed and DRMs were scored according to the 2009 IAS-USA list. Among 43 patients, 38 (88.4%) harbored ?1 DRM. The median time between two sequential resistance tests was 5 months (IQR: 3-10). Thymidine analogue mutations accumulated at a rate of 0.07 mutation per month of drug exposure, which is faster than previously reported. Routine virological monitoring should be implemented in resource-limited settings to preserve susceptibility to second-line regimens.
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Metabolic and anthropometric parameters contribute to ART-mediated CD4+ T cell recovery in HIV-1-infected individuals: an observational study.
J Int AIDS Soc
PUBLISHED: 07-29-2011
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The degree of immune reconstitution achieved in response to suppressive ART is associated with baseline individual characteristics, such as pre-treatment CD4 count, levels of viral replication, cellular activation, choice of treatment regimen and gender. However, the combined effect of these variables on long-term CD4 recovery remains elusive, and no single variable predicts treatment response. We sought to determine if adiposity and molecules associated with lipid metabolism may affect the response to ART and the degree of subsequent immune reconstitution, and to assess their ability to predict CD4 recovery.
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HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study.
Lancet Infect Dis
PUBLISHED: 07-27-2011
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There are few data on the epidemiology of primary HIV-1 drug resistance after the roll-out of antiretroviral treatment (ART) in sub-Saharan Africa. We aimed to assess the prevalence of primary resistance in six African countries after ART roll-out and if wider use of ART in sub-Saharan Africa is associated with rising prevalence of drug resistance.
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Management pathway for patients with cervical cancer in the Auckland region 2003-2007.
J Med Imaging Radiat Oncol
PUBLISHED: 06-24-2011
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This review was performed to describe the patient pathway and timelines involved in the treatment of FIGO (International Federation of Gynecology and Obstetrics) stage IB1 to IVA cervical cancer in a New Zealand cancer centre.
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Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations; two arguments for viral load monitoring in Africa.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 06-23-2011
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This study aimed to investigate the consequences of using clinicoimmunological criteria to detect antiretroviral treatment (ART) failure and guide regimen switches in HIV-infected adults in sub-Saharan Africa. Frequencies of unnecessary switches, patterns of HIV drug resistance, and risk factors for the accumulation of nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were evaluated.
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Comparison of Xpert MTB/RIF with other nucleic acid technologies for diagnosing pulmonary tuberculosis in a high HIV prevalence setting: a prospective study.
PLoS Med.
PUBLISHED: 06-07-2011
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The Xpert MTB/RIF (Cepheid) non-laboratory-based molecular assay has potential to improve the diagnosis of tuberculosis (TB), especially in HIV-infected populations, through increased sensitivity, reduced turnaround time (2 h), and immediate identification of rifampicin (RIF) resistance. In a prospective clinical validation study we compared the performance of Xpert MTB/RIF, MTBDRplus (Hain Lifescience), LightCycler Mycobacterium Detection (LCTB) (Roche), with acid fast bacilli (AFB) smear microscopy and liquid culture on a single sputum specimen.
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Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy.
Antivir. Ther. (Lond.)
PUBLISHED: 05-29-2011
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The emergence of complex HIV-1 drug resistance mutations has been linked to the duration of time patients are on a failing antiretroviral drug regimen. This study reports on resistance profiles in a closely monitored subtype C infected cohort.
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The net cost of incorporating resistance testing into HIV/AIDS treatment in South Africa: a Markov model with primary data.
J Int AIDS Soc
PUBLISHED: 05-15-2011
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Current guidelines for providing antiretroviral therapy (ART) in South Africas public sector programme call for switching patients from first-line to second-line treatment upon virologic failure as indicated by two consecutive viral loads above 5000 copies/ml, but without laboratory evidence of viral resistance. We modelled the net cost of adding resistance testing for patients with virological failure and retaining patients without resistance on first-line therapy, rather than switching all failures to second-line therapy.
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Increased microbial translocation in ? 180 days old perinatally human immunodeficiency virus-positive infants as compared with human immunodeficiency virus-exposed uninfected infants of similar age.
Pediatr. Infect. Dis. J.
PUBLISHED: 05-10-2011
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The effect of early versus deferred antiretroviral treatment (ART) on plasma concentration of lipopolysaccharide (LPS) and host LPS-binding molecules in human immunodeficiency virus (HIV)-infected infants up to 1 year of age was investigated.
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Utility of clinical parameters to identify HIV infection in infants below ten weeks of age in South Africa: a prospective cohort study.
BMC Pediatr
PUBLISHED: 04-26-2011
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As HIV-infected infants have high mortality, the World Health Organization now recommends initiating antiretroviral therapy as early as possible in the first year of life. However, in many settings, laboratory diagnosis of HIV in infants is not readily available. We aimed to develop a clinical algorithm for HIV presumptive diagnosis in infants < 10 weeks old using screening data from the Children with HIV Early Antiretroviral therapy (CHER) study in South Africa.HIV-infected and HIV-uninfected exposed infants < 10 weeks of age were identified through Vertical Transmission Prevention programs. Clinical and laboratory data were systematically recorded, groups were compared using Kruskal-Wallis, analysis of variance (ANOVA), and Fishers exact tests. Receiver Operating Characteristic (ROC) curves were compiled using combinations of clinical findings.
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Patterns of care for cervical cancer in Auckland, New Zealand, 2003-2007.
J Med Imaging Radiat Oncol
PUBLISHED: 03-09-2011
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The purpose of this review is to document current patterns of care for the International Federation of Gynecology and Obstetrics (FIGO) stage IB1 to IVA cervical cancer in a New Zealand cancer centre.
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Changing pattern of lymphoma subgroups at a tertiary academic complex in a high-prevalence HIV setting: a South African perspective.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-18-2011
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HIV infection has been associated with an increased risk of non-Hodgkin lymphoma, particularly in the first world. Despite the high burden of HIV infection in sub-Saharan regions, published data on HIV and malignancies are sparse from these areas.
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Transmitted HIV type 1 drug resistance among individuals with recent HIV infection in East and Southern Africa.
AIDS Res. Hum. Retroviruses
PUBLISHED: 11-23-2010
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To characterize WHO-defined transmitted HIV drug resistance mutation (TDRM) data from recently HIV-infected African volunteers, we sequenced HIV (pol) and evaluated for TDRM the earliest available specimens from ARV-naive volunteers diagnosed within 1 year of their estimated date of infection at eight research centers in sub-Saharan Africa. TDRMs were detected in 19/408 (5%) volunteers. The prevalence of TDRMs varied by research center, from 5/26 (19%) in Entebbe, 6/78 (8%) in Kigali, 2/49 (4%) in Kilifi, to 3/106 (3%) in Lusaka. One of five volunteers from Cape Town (20%) had TDRMs. Despite small numbers, our data suggest an increase in DRMs by year of infection in Zambia (p?=?0.004). The prevalence observed in Entebbe was high across the entire study. ARV history data from 12 (63%) HIV-infected sexual partners were available; 3 reported ARV use prior to transmission. Among four partners with sequence data available, transmission linkage was confirmed and two had the same TDRMs as the newly infected volunteer (both K103N). As ARV therapy continues to increase in availability throughout Africa, monitoring incident virus strains for the presence of TDRMs should be a priority. Early HIV infection cohorts provide an excellent and important platform to monitor the development of TDRMs to inform treatment guidelines, drug choices, and strategies for secondary prevention of TDRM transmission.
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Xpert(®) MTB/RIF for point-of-care diagnosis of TB in high-HIV burden, resource-limited countries: hype or hope?
Expert Rev. Mol. Diagn.
PUBLISHED: 10-23-2010
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Despite the identification of Mycobacterium tuberculosis as the cause of tuberculosis (TB) more than a century ago, diagnosing TB in resource-poor countries remains a challenge, especially in people living with HIV. In the past decade, important research investments have been made towards the development of new diagnostics for TB and the Xpert(®) MTB/RIF assay (Cepheid, CA, USA) has emerged as one of the most promising. In this article, we review the current knowledge on Xpert MTB/RIF, discuss the potential value of Xpert MTB/RIF as a point-of-care diagnostic for drug-sensitive and drug-resistant TB, and outline the potential indications for the assay in resource-limited, high-HIV burden settings. We also discuss key research questions that need to be addressed prior to possible large-scale implementation of the assay.
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A comparative analysis of HIV drug resistance interpretation based on short reverse transcriptase sequences versus full sequences.
AIDS Res Ther
PUBLISHED: 08-04-2010
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As second-line antiretroviral treatment (ART) becomes more accessible in resource-limited settings (RLS), the need for more affordable monitoring tools such as point-of-care viral load assays and simplified genotypic HIV drug resistance (HIVDR) tests increases substantially. The prohibitive expenses of genotypic HIVDR assays could partly be addressed by focusing on a smaller region of the HIV reverse transcriptase gene (RT) that encompasses the majority of HIVDR mutations for people on ART in RLS. In this study, an in silico analysis of 125,329 RT sequences was performed to investigate the effect of submitting short RT sequences (codon 41 to 238) to the commonly used virco®TYPE and Stanford genotype interpretation tools.
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Multi-analyte profiling of ten cytokines in South African HIV-infected patients with Immune Reconstitution Inflammatory Syndrome (IRIS).
AIDS Res Ther
PUBLISHED: 07-13-2010
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Immune reconstitution inflammatory syndrome (IRIS) is an important complication of HAART in sub-Saharan Africa, where opportunistic infections (OIs) including mycobacteria and cryptococcus are common. The immune systems role in HIV infected patients is complex with cytokine expression strongly influencing HIV infection and replication.
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Should South Africa be performing nucleic acid testing on HIV enzyme-linked immunosorbent assay-negative samples?
J. Clin. Microbiol.
PUBLISHED: 07-07-2010
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The frequency of acute HIV infection (AHI) among HIV-1 enzyme-linked immunosorbent assay (ELISA)-negative samples received from general hospital patient admissions was assessed. Of 3,005 samples pooled for nucleic acid testing, a prevalence of 0.13% was found. Pooled nucleic acid testing may be feasible for low-cost identification of AHI in high-prevalence settings.
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HIV-1 drug resistance mutations are present in six percent of persons initiating antiretroviral therapy in Lusaka, Zambia.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 06-30-2010
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To assess the mutational patterns and factors associated with baseline drug-resistant HIV-1 present at initiation of first-line antiretroviral therapy (ART) at 3 sites in Lusaka, Zambia, in 2007-2008.
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Nurse versus doctor management of HIV-infected patients receiving antiretroviral therapy (CIPRA-SA): a randomised non-inferiority trial.
Lancet
PUBLISHED: 06-19-2010
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Expanded access to combination antiretroviral therapy (ART) in resource-poor settings is dependent on task shifting from doctors to other health-care providers. We compared outcomes of nurse versus doctor management of ART care for HIV-infected patients.
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Abbott RealTime HIV-1 m2000rt viral load testing: manual extraction versus the automated m2000sp extraction.
J. Virol. Methods
PUBLISHED: 06-11-2010
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The Abbott RealTime HIV-1 assay is a real-time nucleic acid amplification assay available for HIV-1 viral load quantitation. The assay has a platform for automated extraction of viral RNA from plasma or dried blood spot samples, and an amplification platform with real time fluorescent detection. Overall, this study found no clinically relevant differences in viral load, if samples were extracted manually.
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Estimating the impact of plasma HIV-1 RNA reductions on heterosexual HIV-1 transmission risk.
PLoS ONE
PUBLISHED: 06-10-2010
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The risk of sexual transmission of HIV-1 is strongly associated with the level of HIV-1 RNA in plasma making reduction in HIV-1 plasma levels an important target for HIV-1 prevention interventions. A quantitative understanding of the relationship of plasma HIV-1 RNA and HIV-1 transmission risk could help predict the impact of candidate HIV-1 prevention interventions that operate by reducing plasma HIV-1 levels, such as antiretroviral therapy (ART), therapeutic vaccines, and other non-ART interventions.
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Stabilization of HIV-1 gp120-CD4 receptor complex through targeted interchain disulfide exchange.
J. Biol. Chem.
PUBLISHED: 06-10-2010
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HIV-1 enters cells via interaction between the trimeric envelope (Env) glycoprotein gp120/gp41 and the host cell surface receptor molecule CD4. The requirement of CD4 for viral entry has rationalized the development of recombinant CD4-based proteins as competitive viral attachment inhibitors and immunotherapeutic agents. In this study, we describe a novel recombinant CD4 protein designed to bind gp120 through a targeted disulfide-exchange mechanism. According to structural models of the gp120-CD4 receptor complex, substitution of Ser(60) on the CD4 domain 1 alpha-helix with Cys positions a thiol in proximity of the gp120 V1/V2 loop disulfide (Cys(126)-Cys(196)), satisfying the stereochemical and geometric conditions for redox exchange between CD4 Cys(60) and gp120 Cys(126), and the consequent formation of an interchain disulfide bond. In this study, we provide experimental evidence for this effect by describing the expression, purification, refolding, receptor binding and antiviral activity analysis of a recombinant two-domain CD4 variant containing the S60C mutation (2dCD4-S60C). We show that 2dCD4-S60C binds HIV-1 gp120 with a significantly higher affinity than wild-type protein under conditions that facilitate disulfide exchange and that this translates into a corresponding increase in the efficacy of CD4-mediated viral entry inhibition. We propose that targeted redox exchange between conserved gp120 disulfides and nucleophilic moieties positioned strategically on CD4 (or CD4-like scaffolds) conceptualizes a new strategy in the development of high affinity HIV-1 Env ligands, with important implications for therapy and vaccine development. More generally, this chalcogen substitution approach provides a general means of stabilizing receptor-ligand complexes where the structural and biophysical conditions for disulfide exchange are satisfied.
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Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis.
Lancet
PUBLISHED: 05-26-2010
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High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners.
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Protease Inhibitor Resistance Is Uncommon in HIV-1 Subtype C Infected Patients on Failing Second-Line Lopinavir/r-Containing Antiretroviral Therapy in South Africa.
AIDS Res Treat
PUBLISHED: 05-16-2010
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Limited data exist on HIV-1 drug resistance patterns in South Africa following second-line protease-inhibitor containing regimen failure. This study examined drug resistance patterns emerging in 75 HIV-1 infected adults experiencing virologic failure on a second-line regimen containing 2 NRTI and lopinavir/ritonavir. Ninety six percent of patients (n = 72) were infected with HIV-1 subtype C, two patients were infected with HIV-1 subtype D and one with HIV-1 subtype A1. Thirty nine percent (n = 29) of patients had no resistance mutations in protease or reverse transcriptase suggesting that medication non-adherence was a major factor contributing to failure. Major lopinavir resistance mutations were infrequent (5 of 75; 7%), indicating that drug resistance is not the main barrier to future viral suppression.
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FOXP3 expression is upregulated in CD4T cells in progressive HIV-1 infection and is a marker of disease severity.
PLoS ONE
PUBLISHED: 04-13-2010
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Understanding the role of different classes of T cells during HIV infection is critical to determining which responses correlate with protective immunity. To date, it is unclear whether alterations in regulatory T cell (Treg) function are contributory to progression of HIV infection.
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Natural polymorphisms of integrase among HIV type 1-infected South African patients.
AIDS Res. Hum. Retroviruses
PUBLISHED: 04-10-2010
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An HIV-1 subtype C specific assay was established for integrase genotyping from 51 integrase inhibitor-naive patient plasma samples and 22 antiretroviral drug-naive primary viral isolates from South Africa. Seventy-one of the 73 samples were classified as HIV-1 subtype C and two samples were unique AC and CG recombinants in integrase. Amino acid sequence analysis revealed there were no primary mutations (Y143R/C/H, Q148H/R/K, and N155H/S) associated with reduced susceptibility to the integrase inhibitors raltegravir and elvitegravir. However, one sample had the T97A mutation, three samples had the E157Q and V165I mutations, and the majority of samples contained the polymorphic mutation V72I. The expected finding of no major integrase mutations conferring resistance to integrase inhibitors suggests that this new antiretroviral drug class will be effective in our region where HIV-1 subtype C predominates. However, the impact of E157Q and other naturally occurring polymorphisms warrants further phenotypic investigation.
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Association between HIV replication and serum leptin levels: an observational study of a cohort of HIV-1-infected South African women.
J Int AIDS Soc
PUBLISHED: 04-07-2010
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Advanced HIV infection can result in lipoatrophy and wasting, even in the absence of ongoing opportunistic infections, suggesting that HIV may directly affect adipose tissue amount and distribution.
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Epidemiology of systemic sclerosis.
Best Pract Res Clin Rheumatol
PUBLISHED: 03-16-2010
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Systemic sclerosis (SSc) is a multisystem auto-immune disease. The two main subtypes of SSc (limited and diffuse) typically have differing courses and prognoses. New classification criteria have been proposed to identify SSc in the earliest stages, before skin involvement. Over the past three decades, there has been an apparent increase in the incidence of SSc to approximately 20 per million, possibly due to improved diagnosis. The most extensively studied environmental associations of SSc are organic solvents and silica but no single risk factor has emerged. Recent genetic studies have identified new susceptibility factors including human leucocyte antigen (HLA) haplotypes and polymorphisms in immune regulatory genes. Despite earlier disease recognition and effective treatment for some of its complications, SSc still carries a high mortality, particularly due to cardiorespiratory complications. Although some predictors of organ involvement and outcomes have been identified, novel biomarkers are greatly needed. Due to low disease prevalence, large multicentre research collaborations are required.
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Challenges in implementing HIV load testing in South Africa.
J. Infect. Dis.
PUBLISHED: 03-16-2010
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The South African antiretroviral treatment guidelines recommend the use of human immunodeficiency virus type 1 (HIV-1) load testing for patient monitoring and, in particular, to assist in switching to second-line treatment regimens. There are significant challenges to implementing HIV load testing on the scale that is required in South Africa. To put this in context, approximately 560,000 HIV-infected individuals are receiving antiretroviral therapy, and program recommendations include viral load testing twice per year. Currently, a 3-tiered laboratory infrastructure exists with tertiary facilities and, to some extent, secondary laboratories able to implement quantitative HIV nucleic acid testing. Challenges include high sample volumes, transportation logistics from remote sites, costs, phlebotomy in children, a national skills shortage, and sample throughput of technology platforms. Several approaches are thus being explored simultaneously: (1) the feasibility of establishing higher throughput and more automated central laboratories; (2) improvement of current sample collection, transportation, and storage techniques; (3) alternative viral load technologies, including flow-based marker screening approaches to reduce testing volumes, and (4) point-of-care viral load testing strategies for clinics. The development of appropriate solutions for each laboratory tier in South Africa will require close collaboration between researchers in the field and partners in industry.
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Quantifying HIV for monitoring antiretroviral therapy in resource-poor settings.
J. Infect. Dis.
PUBLISHED: 03-16-2010
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There is increasing evidence to support the inability of CD4 cell count monitoring to predict virological failure in human immunodeficiency virus-infected individuals receiving antiretroviral therapy. There is renewed interest in improving access to viral load monitoring in resource-constrained regions to monitor adherence to treatment and to switch therapy. The field is rapidly changing as new technology platforms are made available for evaluation. This article presents an up to date summary of the assays available for viral load monitoring and suggests approaches for their implementation.
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Characterization of Lymphomas in a high prevalence HIV setting.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 02-18-2010
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HIV infection has been associated with an increased risk of malignancy, both AIDS defining and non-AIDS defining.
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Emergence of drug resistance in HIV-1 subtype C infected children failing the South African national antiretroviral roll-out program.
Pediatr. Infect. Dis. J.
PUBLISHED: 11-26-2009
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HIV-1 drug resistance patterns in 41 children failing antiretroviral therapy in South Africa were examined. Resistance mutation profiles were similar to adults published from the region, with the exception of high rates of lopinavir/r resistance (44%). Ninety-eight percent presented with known drug resistance mutations with M184V (82%) and K103N (44%), the dominant mutations.
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Comparison of focus HerpesSelect and Kalon HSV-2 gG2 ELISA serological assays to detect herpes simplex virus type 2 antibodies in a South African population.
Sex Transm Infect
PUBLISHED: 10-16-2009
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Sero-epidemiological studies of herpes simplex virus (HSV) type 2 infection in Africa remain difficult to interpret as a result of the high rate of false-positive results observed when using the new recombinant gG2 HSV-2 ELISA tests. The performance of two widely used gG2 ELISA was compared to derive an appropriate testing algorithm for use in South Africa.
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Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation.
Blood
PUBLISHED: 10-14-2009
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HIV infection is associated with an increased risk of thrombosis; and as antiretroviral therapy has increased the lifespan of HIV-infected patients, their risk for cardiovascular events is expected to increase. A large clinical study found recently that all-cause mortality for HIV(+) patients was related to plasma levels of interleukin-6 and to D-dimer products of fibrinolysis. We provide evidence that this elevated risk for coagulation may be related to increased proportions of monocytes expressing cell surface tissue factor (TF, thromboplastin) in persons with HIV infection. Monocyte TF expression could be induced in vitro by lipopolysaccharide and flagellin, but not by interleukin-6. Monocyte expression of TF was correlated with HIV levels in plasma, with indices of immune activation, and with plasma levels of soluble CD14, a marker of in vivo lipopolysaccharide exposure. TF levels also correlated with plasma levels of D-dimers, reflective of in vivo clot formation and fibrinolysis. Thus, drivers of immune activation in HIV disease, such as HIV replication, and potentially, microbial translocation, may activate clotting cascades and contribute to thrombus formation and cardiovascular morbidities in HIV infection.
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Evaluation of a dried blood spot HIV-1 RNA program for early infant diagnosis and viral load monitoring at rural and remote healthcare facilities.
AIDS
PUBLISHED: 09-11-2009
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To assess technical and operational performance of a dried blood spot (DBS)-based HIV-1 RNA service for remote healthcare facilities in a low-income country.
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Dried fluid spots for HIV type-1 viral load and resistance genotyping: a systematic review.
Antivir. Ther. (Lond.)
PUBLISHED: 08-26-2009
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Dried spots on filter paper made of whole blood (dried blood spots; DBS), plasma (dried plasma spots; DPS) or serum (dried serum spots) hold promise as an affordable and practical alternative specimen source to liquid plasma for HIV type-1 (HIV-1) viral load determination and drug resistance genotyping in the context of the rapidly expanding access to antiretroviral therapy (ART) for HIV-1-infected individuals in low- and middle-income countries. This report reviews the current evidence for their utility.
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Radiotherapy utilisation in lung cancer in New Zealand: disparities with optimal rates explained.
N. Z. Med. J.
PUBLISHED: 07-16-2009
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The intervention rate (IR) of radiotherapy (RT) is important for health service planning. As actual IRs are commonly lower than those predicted by models, we sought to determine the reasons for this discrepancy, using lung cancer in a mixed urban-rural region of New Zealand (NZ).
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Local reference ranges for full blood count and CD4 lymphocyte count testing.
S. Afr. Med. J.
PUBLISHED: 07-11-2009
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Recent advances in full blood count and CD4 technology, coupled with the changing population demographics of the Gauteng region, have necessitated reevaluation of the reference ranges currently in use.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.