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Find video protocols related to scientific articles indexed in Pubmed.
Activation of HIV Transcription with Short-Course Vorinostat in HIV-Infected Patients on Suppressive Antiretroviral Therapy.
PLoS Pathog.
PUBLISHED: 11-01-2014
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Human immunodeficiency virus (HIV) persistence in latently infected resting memory CD4+ T-cells is the major barrier to HIV cure. Cellular histone deacetylases (HDACs) are important in maintaining HIV latency and histone deacetylase inhibitors (HDACi) may reverse latency by activating HIV transcription from latently infected CD4+ T-cells. We performed a single arm, open label, proof-of-concept study in which vorinostat, a pan-HDACi, was administered 400 mg orally once daily for 14 days to 20 HIV-infected individuals on suppressive antiretroviral therapy (ART). The primary endpoint was change in cell associated unspliced (CA-US) HIV RNA in total CD4+ T-cells from blood at day 14. The study is registered at ClinicalTrials.gov (NCT01365065). Vorinostat was safe and well tolerated and there were no dose modifications or study drug discontinuations. CA-US HIV RNA in blood increased significantly in 18/20 patients (90%) with a median fold change from baseline to peak value of 7.4 (IQR 3.4, 9.1). CA-US RNA was significantly elevated 8 hours post drug and remained elevated 70 days after last dose. Significant early changes in expression of genes associated with chromatin remodeling and activation of HIV transcription correlated with the magnitude of increased CA-US HIV RNA. There were no statistically significant changes in plasma HIV RNA, concentration of HIV DNA, integrated DNA, inducible virus in CD4+ T-cells or markers of T-cell activation. Vorinostat induced a significant and sustained increase in HIV transcription from latency in the majority of HIV-infected patients. However, additional interventions will be needed to efficiently induce virus production and ultimately eliminate latently infected cells.
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Loss to follow-up in the Australian HIV Observational Database.
Antivir. Ther. (Lond.)
PUBLISHED: 10-24-2014
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Loss to follow-up (LTFU) in HIV-positive cohorts is an important surrogate for interrupted clinical care which can potentially influence the assessment of HIV disease status and outcomes. After preliminary evaluation of LTFU rates and patient characteristics, we evaluated the risk of mortality by LTFU status in a high resource setting.
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Incident hepatitis B infection subsequent to the diagnosis of HIV infection in a Melbourne cohort: missed opportunities for prevention.
Sex Health
PUBLISHED: 08-21-2014
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Background The characteristics associated with incident hepatitis B (HBV) infection in HIV-positive individuals are not well described in the Australian setting. The aim of this study is to determine the characteristics of and risk factors for HBV infection within HIV-infected individuals in a Melbourne cohort between 1985 and 2011. Methods: Individuals susceptible to HBV at their HIV diagnosis were identified using their HBV serology stored within the Victorian HIV database. Within this group, those who had a subsequent positive test for hepatitis B surface antigen or hepatitis B core antibody were identified as infected with HBV after their HIV diagnosis. Incident cases were matched with controls from the initially susceptible group who did not seroconvert for analysis. An incidence rate was calculated from the number of seroconversions and the cumulative time at risk (in 1000 patient-years of follow-up). Results: Of the 4711 patients with HIV seen more than once, 3223 had HBV testing. Of the 174 with positive HBV test results, 39 individuals met the definition of seroconversion after HIV diagnosis, representing the incident cases. The estimated HBV incidence rate was 1.81 (95% confidence interval: 1.28-2.47) per 1000 patient-years at risk. These individuals form the basis of a detailed case series and case-control study. Data collected include demographic details, immunological and virological characteristics, antiretroviral treatment and vaccination history. Conclusions: HIV-infected individuals should be screened for HBV and monitored for incident infection. Optimal control of HIV and improved vaccination coverage provide the best opportunity for prevention.
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Hepatitis E in Australian HIV-infected patients: an under-recognised pathogen?
Sex Health
PUBLISHED: 07-30-2014
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Background Hepatitis E virus (HEV) infection has been found to cause chronic hepatitis in HIV-infected patients. In Australia, where HEV is nonendemic, background seroprevalence is reportedly low but has not been evaluated in the HIV-infected population. The study aimed to assess the seroprevalence of HEV in a cohort of HIV-infected patients with normal liver function and in another group with biochemical hepatitis.
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Bone mineral density over 96 weeks in adults failing first-line therapy randomized to raltegravir/lopinavir/ritonavir compared with standard second-line therapy.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 07-30-2014
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To compare bone mineral density (BMD) changes over 96 weeks in adults virologically failing standard first-line therapy, randomized to raltegravir plus lopinavir/ritonavir (RAL + LPV/r) or conventional 2-3 nucleoside/nucleotide reverse transcriptase inhibitors [N(t)RTIs] + LPV/r second-line therapy.
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Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel.
JAMA
PUBLISHED: 07-20-2014
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New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV).
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Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion.
Neuron
PUBLISHED: 06-12-2014
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Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR's effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion.
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Recent trends in early stage response to combination antiretroviral therapy in Australia.
Antivir. Ther. (Lond.)
PUBLISHED: 03-16-2014
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There have been improvements in combination antiretroviral therapy (cART) over the last 15 years. The aim of this analysis was to assess whether improvements in ART have resulted in improvements in surrogates of HIV outcome.
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Determinants of viremia copy-years in people with HIV/AIDS after initiation of antiretroviral therapy.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-28-2014
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Recent studies suggest higher cumulative HIV viremia exposure measured as viremia copy-years (VCY) is associated with increased all-cause mortality. The objectives of this study are (1) report the association between VCY and all-cause mortality and (2) assess associations between common patient characteristics and VCY.
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Determinants of developing widened spatial QRS-T angle in HIV-infected individuals: results from the Strategies for Management of Antiretroviral Therapy [SMART] Study.
J Electrocardiol
PUBLISHED: 01-11-2014
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A widened electrocardiographic spatial QRS-T angle has been shown to be predictive of cardiovascular disease in HIV-infected individuals. However, determinants and risk factors of developing widened QRS-T angle over time in this population remain unknown.
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Plasma lipidomic profiling of treated HIV-positive individuals and the implications for cardiovascular risk prediction.
PLoS ONE
PUBLISHED: 01-01-2014
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The increased risk of coronary artery disease in human immunodeficiency virus (HIV) positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV-positive patients.
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Determinants of suicide and accidental or violent death in the Australian HIV Observational Database.
PLoS ONE
PUBLISHED: 01-01-2014
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Rates of suicide and accidental or violent death remain high in HIV-positive populations despite significantly improved prognosis since the introduction of cART.
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The inside story. Physicians views on digital ano-rectal examination for anal cancer screening of HIV positive men who have sex with men.
J Med Screen
PUBLISHED: 12-06-2013
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Anal cancer is relatively common amongst HIV positive men who have sex with men (MSM), but little is known about the anal cancer screening practices of HIV physicians, and whether digital ano-rectal examination (DARE) is utilized for this. To determine the practice of anal cancer screening among HIV physicians, and to identify any barriers for implementing DARE as a method for anal cancer screening.
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Bone mineral density in HIV participants randomized to raltegravir and lopinavir/ritonavir compared with standard second line therapy.
AIDS
PUBLISHED: 08-08-2013
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To compare changes over 48 weeks in bone mineral density (BMD) between participants randomized to lopinavir/ritonavir (LPV/r) + raltegravir (RAL) or LPV/r + 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second line therapy.
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Abacavir exposure and cardiovascular risk factors in HIV-positive patients with coronary heart disease: a retrospective case-control study.
Sex Health
PUBLISHED: 07-03-2013
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Background HIV-positive patients have an estimated twofold increased risk of acute myocardial infarction and coronary heart disease (CHD). While traditional cardiovascular risk factors and the effects of HIV and chronic inflammation all play a role, the contribution of long-term exposure to antiretroviral (ARV) agents is becoming clear. Methods: We performed a retrospective case-control study of HIV-positive patients seen from January 1996 to December 2009 to evaluate the impact of HIV suppression and exposure to specific ARVs on the incidence of CHD. Results: Cases (n=68) were HIV-positive with evidence of CHD. Two age- and sex-matched HIV-positive controls (n=136) without a diagnosis of CHD were assigned for each case. The cumulative incidence of CHD in the period covered by the study was 3.8%, with an incidence of 8.5 cases per 1000 patient-years of follow up. Cases had an increased likelihood of having hypertension (odds ratio (OR): 6.62, P<0.001), a family history of CHD (OR: 5.82, P<0.001), lower high-density lipoprotein levels (OR: 0.28, P=0.025) and higher Framingham risk scores compared with controls. Following adjustment for traditional cardiovascular risk factors, the presence of CHD was significantly associated with the current use of abacavir (OR: 2.10, P=0.03). Protease inhibitor therapy, HIV viral load and duration of known HIV infection were not predictive of CHD in our patient population. Conclusions: Our data add to the evidence that abacavir use is associated with CHD in HIV-positive patients in Australia.
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Improved neurocognitive test performance in both arms of the SMART study: impact of practice effect.
J. Neurovirol.
PUBLISHED: 06-18-2013
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We evaluated factors associated with improvement in neurocognitive performance in 258 HIV-infected adults with baseline CD4 lymphocyte counts above 350 cells/mm³ randomized to intermittent, CD4-guided antiretroviral therapy (ART) (128 participants) versus continuous therapy (130) in the Neurology substudy of the Strategies for Management of Antiretroviral Therapy trial. Participants were enrolled in Australia, North America, Brazil, and Thailand, and neurocognitive performance was assessed by a five-test battery at baseline and month 6. The primary outcome was change in the quantitative neurocognitive performance z score (QNPZ-5), the average of the z scores of the five tests. Associations of the 6-month change in test scores with ART use, CD4 cell counts, HIV RNA levels, and other factors were determined using multiple regression models. At baseline, median age was 40 years, median CD4 cell count was 513 cells/mm³, 88 % had plasma HIV RNA ? 400 copies/mL, and mean QNPZ-5 was -0.68. Neurocognitive performance improved in both treatment groups by 6 months; QNPZ-5 scores increased by 0.20 and 0.13 in the intermittent and continuous ART groups, respectively (both P < 0.001 for increase and P = 0.26 for difference). ART was used on average for 3.6 and 5.9 out of the 6 months in the intermittent and continuous ART groups, respectively, but the increase in neurocognitive test scores could not be explained by ART use, changes in CD4, or plasma HIV RNA, which suggests a practice effect. The impact of a practice effect after 6 months emphasizes the need for a control group in HIV studies that measure intervention effects using neurocognitive tests similar to ours.
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Neuroligin1 drives synaptic and behavioral maturation through intracellular interactions.
J. Neurosci.
PUBLISHED: 05-31-2013
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In vitro studies suggest that the intracellular C terminus of Neuroligin1 (NL1) could play a central role in the maturation of excitatory synapses. However, it is unknown how this activity affects synapses in vivo, and whether it may impact the development of complex behaviors. To determine how NL1 influences the state of glutamatergic synapses in vivo, we compared the synaptic and behavioral phenotypes of mice overexpressing a full-length version of NL1 (NL1FL) with mice overexpressing a version missing part of the intracellular domain (NL1?C). We show that overexpression of full-length NL1 yielded an increase in the proportion of synapses with mature characteristics and impaired learning and flexibility. In contrast, the overexpression of NL1?C increased the number of excitatory postsynaptic structures and led to enhanced flexibility in mnemonic and social behaviors. Transient overexpression of NL1FL revealed that elevated levels are not necessary to maintain synaptic and behavioral states altered earlier in development. In contrast, overexpression of NL1FL in the fully mature adult was able to impair normal learning behavior after 1 month of expression. These results provide the first evidence that NL1 significantly impacts key developmental processes that permanently shape circuit function and behavior, as well as the function of fully developed neural circuits. Overall, these manipulations of NL1 function illuminate the significance of NL1 intracellular signaling in vivo, and enhance our understanding of the factors that gate the maturation of glutamatergic synapses and complex behavior. This has significant implications for our ability to address disorders such as autism spectrum disorders.
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Associations between surface markers on blood monocytes and carotid atherosclerosis in HIV-positive individuals.
Immunol. Cell Biol.
PUBLISHED: 05-26-2013
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Chronic HIV infection is associated with increased risk of cardiovascular disease (CVD), including in patients with virological suppression. Persistent innate immune activation may contribute to the development of CVD via activation of monocytes in these patients. We investigated whether changes in monocyte phenotype predict subclinical atherosclerosis in virologically suppressed HIV-positive individuals with low cardiovascular risk. We enroled 51 virologically suppressed HIV-positive individuals not receiving protease inhibitors or statins and 49 age-matched uninfected controls in this study. Carotid artery intima-media thickness (cIMT) was used as a surrogate marker for CVD, and traditional risk factors, including Framingham risk scores, were recorded. Markers of monocyte activation (CD14, CD16, CCR2, CX3CR1, CD38, HLA-DR and CD11b) were measured in whole-blood samples by flow cytometry. Associations were assessed using univariate and multivariate median regressions. Median cIMT was similar between HIV-positive and HIV-negative participants (P=0.3), although HIV-positive patients had significantly higher Framingham risk score (P=0.009) and systemic inflammation. Expression of two monocyte markers, CD11b and CX3CR1, independently predicted carotid artery thickness in HIV-positive individuals after controlling for Framingham risk score (P=0.025 and 0.015, respectively). These markers were not predictive of carotid artery thickening in controls. Our study indicates that monocyte surface markers may serve as novel predictors of CVD in HIV-positive individuals and is consistent with an important role for monocyte activation in the progression of HIV-related cardiovascular pathology.Immunology and Cell Biology advance online publication, 3 December 2013; doi:10.1038/icb.2013.84.
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The great medical imitator: a case of syphilitic osteitis in the setting of HIV infection.
Sex Health
PUBLISHED: 04-06-2013
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A 44-year-old man with well-controlled HIV presented with low-grade fever, pharyngitis, frontal headache, abdominal and shin pain, and abnormal liver function tests 8 weeks after switching from zidovudine to abacavir (while continuing nevirapine and lamivudine). An abacavir reaction was the working diagnosis and thus his antiretroviral regimen was returned to the previously tolerated combination and he received 10 days of oral penicillin (500mg twice daily) for presumptive tonsillitis with significant improvement. A whole-body bone scan demonstrated multiple foci of increased patchy osteoblastic activity of the long bones and skull. Six months later during routine screening, a syphilis rapid plasma reagin (RPR) titre of 128 was detected. Retrospective testing on stored samples demonstrated a first positive RPR at the time of symptomatic presentation. He received three injections of 1.8g benzathine penicillin on a weekly basis with a subsequent decrease in RPR titre and normalisation of the bone scan. Although syphilitic osteitis is rare, this case re-emphasises the importance of considering syphilis when HIV-infected patients present with unusual symptoms. The use of bone scan in this setting and treatment options are discussed.
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The effect of HIV infection on atherosclerosis and lipoprotein metabolism: a one year prospective study.
Atherosclerosis
PUBLISHED: 04-02-2013
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HIV infection is associated with dyslipidaemia and increased risk of cardiovascular disease. The effects of HIV infection and antiretroviral treatment on surrogate markers of atherosclerosis, and lipoprotein metabolism were evaluated in a 12 month prospective study.
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Factors associated with virological failure in a cohort of combination antiretroviral therapy-treated patients managed at a tertiary referral centre.
Sex Health
PUBLISHED: 03-30-2013
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Recent antiretroviral regimens are potent and better tolerated, resulting in a low prevalence of treatment failure. It is important to identify the drivers of virological failure, so that patients at risk can be identified early and prevention strategies implemented.
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Patterns and causes of suboptimal response to tenofovir-based therapy in individuals coinfected with HIV and hepatitis B virus.
Clin. Infect. Dis.
PUBLISHED: 01-11-2013
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Tenofovir (TDF) is effective for treatment of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) infection; however, some individuals have ongoing HBV viremia, the reasons for which are unclear. We determined the patterns and factors associated with detectable HBV DNA in HIV-HBV-coinfected subjects on highly active antiretroviral therapy (HAART).
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Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy.
J. Bone Miner. Res.
PUBLISHED: 01-10-2013
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Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (?CTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p ? 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and ?CTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months.
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HIV Lipodystrophy in Participants Randomised to Lopinavir/Ritonavir (LPV/r) +2-3 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) or LPV/r + Raltegravir as Second-Line Antiretroviral Therapy.
PLoS ONE
PUBLISHED: 01-01-2013
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To compare changes over 48 weeks in body fat, lipids, Metabolic Syndrome and cardiovascular disease risk between patients randomised 1?1 to lopinavir/ritonavir (r/LPV) plus raltegravir (RAL) compared to r/LPV plus 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second-line therapy.
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Rates and factors associated with major modifications to first-line combination antiretroviral therapy: results from the Asia-Pacific region.
PLoS ONE
PUBLISHED: 01-01-2013
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In the Asia-Pacific region many countries have adopted the WHOs public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART) in resource-rich and resource-limited countries in the region.
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Outcomes from the first assisted reproduction program for HIV-serodiscordant couples in Australia.
Med. J. Aust.
PUBLISHED: 11-24-2011
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To describe the clinical outcomes for all HIV-serodiscordant couples attending an assisted reproduction program.
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Inflammation predicts changes in high-density lipoprotein particles and apolipoprotein A1 following initiation of antiretroviral therapy.
AIDS
PUBLISHED: 08-23-2011
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The effects of HIV infection and antiretroviral therapy (ART) on usual lipid levels have been reported. The effects of initiating versus deferring ART on high-density and low-density lipoprotein particle (HDL-P and LDL-P, respectively) concentrations and apolipoprotein (Apo) levels are not well described.
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CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 06-10-2011
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To examine CD4 cell responses to combination antiretroviral therapy (cART) in patients enrolled in the Australian HIV Observational Database who commenced cART at CD4 cell counts >350 cells per microliter.
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Symptomatic and asymptomatic early neurosyphilis in HIV-infected men who have sex with men: a retrospective case series from 2000 to 2007.
Sex Health
PUBLISHED: 05-20-2011
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The rise in serious complications of early syphilis, including neurosyphilis, particularly in those with HIV infection and in men who have sex with men (MSM), is of concern.
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HIV seroconversions among male non-occupational post-exposure prophylaxis service users: a data linkage study.
Sex Health
PUBLISHED: 05-20-2011
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Despite widespread prescription of non-occupational post-exposure prophylaxis (NPEP) in Victoria, little is known about subsequent HIV acquisition among NPEP users. We linked the Victorian NPEP Service (VNPEPS) database and the Victorian HIV Surveillance Registry to determine the number, incidence rate and predictive factors of HIV seroconversions among users of the VNPEPS.
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Clinical predictors of immune reconstitution following combination antiretroviral therapy in patients from the Australian HIV Observational Database.
PLoS ONE
PUBLISHED: 05-08-2011
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A small but significant number of patients do not achieve CD4 T-cell counts >500 cells/µl despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART.
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Bone, fracture and frailty.
Curr Opin HIV AIDS
PUBLISHED: 05-04-2011
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This review details recent findings from cohort studies that inform the prevalence, incidence and effects of antiretroviral therapy (ART) and HIV infection on low bone mineral density (BMD), osteoporosis and fractures in different populations of HIV-infected individuals. Although ART has been spectacularly effective in prevention of disease progression and improvement in survival, the effects of ART on bone health require more research.
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Low CD4 count is associated with an increased risk of fragility fracture in HIV-infected patients.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 04-28-2011
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Low bone mineral density in HIV-infected patients is an increasingly recognized clinical problem. The aim of this study was to determine the incidence, prevalence, and risk factors for development of low trauma or fragility fractures in an HIV-infected population.
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The Clinical Significance of CD4 Counts in Asian and Caucasian HIV-Infected Populations: Results from TAHOD and AHOD.
J Int Assoc Physicians AIDS Care (Chic)
PUBLISHED: 04-20-2011
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The significance of interethnic variation in CD4 counts between Asian and Caucasian populations is not known. Patients on combination antiretroviral therapy from Treat Asia and Australian HIV Observational Databases (TAHOD, predominantly Asian, n = 3356; and AHOD, predominantly Caucasian, n = 2312, respectively) were followed for 23 144 person-years for AIDS/death and all-cause mortality endpoints. We calculated incidence-rates and used adjusted Cox regression to test for the interaction between cohort (TAHOD/AHOD) and time-updated CD4 count category (lagged by 3 months) for each of the endpoints. There were 382 AIDS/death events in TAHOD (rate: 4.06, 95%CI: 3.68-4.50) and 305 in AHOD (rate: 2.39, 95%CI: 2.13-2.67), per 100 person-years. At any given CD4 count category, the incidence-rates of endpoints were found to be similar between TAHOD and AHOD (in the adjusted models, P > .05 for the interaction term between cohort type and latest CD4 counts). At any given CD4 count, risk of AIDS or death was not found to vary by ethnicity, suggesting that the CD4 count thresholds for predicting outcomes defined in Caucasian populations may be equally valid in Asian populations.
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Biomarkers of immune dysfunction following combination antiretroviral therapy for HIV infection.
Biomark Med
PUBLISHED: 04-09-2011
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Combination antiretroviral therapy (cART) has significantly reduced morbidity and mortality of HIV-infected patients, yet their life expectancy remains reduced compared with the general population. Most HIV-infected patients receiving cART have some persistent immune dysfunction characterized by chronic immune activation and premature aging of the immune system. Here we review biomarkers of T-cell activation (CD69, -25 and -38, HLA-DR, and soluble CD26 and -30); generalized immune activation (C-reactive protein, IL-6 and D-dimer); microbial translocation (lipopolysaccharide, 16S rDNA, lipopolysaccharide-binding protein and soluble CD14); and immune dysfunction of specific cellular subsets (T cells, natural killer cells and monocytes) in HIV-infected patients on cART and their relationship to adverse clinical outcomes including impaired CD4 T-cell recovery, as well as non-AIDS clinical events, such as cardiovascular disease.
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Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis.
Antivir. Ther. (Lond.)
PUBLISHED: 03-31-2011
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Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate.
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Both CD31(+) and CD31? naive CD4(+) T cells are persistent HIV type 1-infected reservoirs in individuals receiving antiretroviral therapy.
J. Infect. Dis.
PUBLISHED: 10-27-2010
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Naive T cell recovery is critical for successful immune reconstitution after antiretroviral therapy (ART), but the relative contribution of CD31(+) and CD31? naive T cells to immune reconstitution and viral persistence is unknown.
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Development of diagnostic criteria for serious non-AIDS events in HIV clinical trials.
HIV Clin Trials
PUBLISHED: 10-27-2010
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Serious non-AIDS (SNA) diseases are important causes of morbidity and mortality in the HAART era. We describe development of standard criteria for 12 SNA events for Endpoint Review Committee (ERC) use in START, a multicenter international HIV clinical trial.
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Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor ? and microbial translocation.
J. Infect. Dis.
PUBLISHED: 09-04-2010
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Multiple host factors may influence CD4(+) T cell reconstitution in human immunodeficiency virus (HIV)-infected patients after suppressive antiretroviral therapy (ART). We hypothesized that residual immune activation and polymorphisms in the interleukin 7 (IL-7) receptor ? (IL-7R?) gene were important for immune recovery.
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Changes in lipids and lipoprotein particle concentrations after interruption of antiretroviral therapy.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 07-27-2010
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The effect of interruption of antiretroviral therapy (ART) on lipoprotein particle subclasses has not been studied. We examined short-term changes in lipids and lipoprotein particles among 332 HIV-infected individuals randomized to interrupt or continue ART in the "Strategies for Management of Antiretroviral Therapy" trial.
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Efficacy and safety of darunavir/ritonavir in treatment-experienced HIV type-1 patients in the POWER 1, 2 and 3 trials at week 96.
Antivir. Ther. (Lond.)
PUBLISHED: 10-09-2009
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Long-term (96-week) efficacy and safety of the protease inhibitor (PI) darunavir coadministered with low-dose ritonavir (DRV/r) was evaluated in HIV type-1 (HIV-1)-infected patients with extensive prior treatment experience in the POWER 1, 2 and 3 trials.
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A randomized, placebo-controlled, dose-escalation study to determine the safety, tolerability, and immunogenicity of an HPV-16 therapeutic vaccine in HIV-positive participants with oncogenic HPV infection of the anus.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-08-2009
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Study aimed to assess safety, tolerability, and immunogenicity of novel therapeutic HPV-16 E6E7 ISCOMATRIX vaccine for treatment of human papilloma virus (HPV)-related anal intraepithelial neoplasia in HIV-infected men who have sex with men with moderate immunosuppression.
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Continuous antiretroviral therapy decreases bone mineral density.
AIDS
PUBLISHED: 06-18-2009
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To assess the effects of antiretroviral therapy (ART) on bone mineral density (BMD) DESIGN: Randomized comparison of continuous ART (viral suppression group; VS) with intermittent ART (drug conservation group; DC) SETTING: Outpatient clinics in the United States, Australia, and Spain.
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Long-term patterns in CD4 response are determined by an interaction between baseline CD4 cell count, viral load, and time: The Asia Pacific HIV Observational Database (APHOD).
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-02-2009
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Random effects models were used to explore how the shape of CD4 cell count responses after commencing combination antiretroviral therapy (cART) develop over time and, in particular, the role of baseline and follow-up covariates.
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An HIV-1 integrase genotype assay for the detection of drug resistance mutations.
Sex Health
PUBLISHED: 04-21-2009
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The integrase inhibitors (e.g. Raltegravir) are a new class of antiretroviral drugs that have recently become available for the treatment of patients with multi-drug resistant HIV-1 within Australia. The emergence of mutations that confer resistance to the integrase inhibitors has been observed in vivo; however, no commercial genotyping assay is currently available to screen for resistance to these drugs.
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Lipoprotein particle subclasses, cardiovascular disease and HIV infection.
Atherosclerosis
PUBLISHED: 03-03-2009
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To study the association of lipoprotein particles with CVD in a subgroup of HIV-infected patients who were enrolled in the Strategies for Management of Anti-Retroviral Therapy (SMART) study. SMART was a trial of intermittent use of ART (drug conservation [DC]) versus continuous of ART (viral suppression [VS]).
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SynCAM1 recruits NMDA receptors via protein 4.1B.
Mol. Cell. Neurosci.
PUBLISHED: 02-19-2009
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Cell adhesion molecules have been implicated as key organizers of synaptic structures, but there is still a need to determine how these molecules facilitate neurotransmitter receptor recruitment to developing synapses. Here, we identify erythrocyte protein band 4.1-like 3 (protein 4.1B) as an intracellular effector molecule of Synaptic Cell Adhesion Molecule 1 (SynCAM1) that is sufficient to recruit NMDA-type receptors (NMDARs) to SynCAM1 adhesion sites in COS7 cells. Protein 4.1B in conjunction with SynCAM1 also increased the frequency of NMDAR-mediated mEPSCs and area of presynaptic contact in an HEK293 cell/ neuron co-culture assay. Studies in cultured hippocampal neurons reveal that manipulation of protein 4.1B expression levels specifically affects NMDAR-mediated activity and localization. Finally, further experimentation in COS7 cells show that SynCAM1 may also interact with protein 4.1N to specifically effect AMPA type receptor (AMPAR) recruitment. Thus, SynCAM1 may recruit both AMPARs and NMDARs by independent mechanisms during synapse formation.
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Successful treatment of Epstein-Barr virus encephalitis in the setting of HIV-associated neurocognitive disorder: a diagnostic and therapeutic challenge.
Antivir. Ther. (Lond.)
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We report a challenging case of HIV-associated neurocognitive disorder with superimposed Epstein-Barr virus (EBV) encephalitis. The patient presented with an abnormal MRI brain scan, and EBV DNA that was detected in the cerebrospinal fluid and brain biopsy, which also demonstrated histopathological findings consistent with the diagnosis. This occurred on the background of a 12-month period of gradual cognitive decrease secondary to HIV-associated dementia. Invasive testing was required to reach the diagnosis in this case, highlighting the importance of thorough investigation of neurological impairment in HIV-positive patients. Clinicopathological recovery was achieved through optimization of antiretroviral therapy and use of valganciclovir.
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Electrocardiographic spatial QRS-T angle and incident cardiovascular disease in HIV-infected patients (from the Strategies for the Management of Antiretroviral Therapy [SMART] study).
Am. J. Cardiol.
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Widening of the electrocardiographic (ECG) spatial QRS-T angle has been predictive of cardiovascular disease (CVD) events in the general population. However, its prognostic significance in human immunodeficiency virus (HIV)-infected patients remains unknown. The spatial QRS-T angle was derived from the baseline resting 12-lead electrocardiogram of 4,453 HIV-infected patients aged 43.5 ± 9.3 years from the Strategies for Management of Antiretroviral Therapy (SMART) trial. CVD events were identified during a median follow-up of 28.7 months. Quartiles of the spatial QRS-T angle was calculated for men and women separately, and values in the upper quartile were considered as a widened angle (values >74° for women and >93° for men). A multivariate Cox proportional hazards analysis was used to examine the association between a widened baseline spatial QRS-T angle and incident CVD events. During 11,965 person-years of follow-up, 152 CVD events occurred at a rate of 1.27 events/100 person-years. The rate of CVD events in those with a widened spatial QRS-T angle was almost double the rate in those with a normal spatial QRS-T angle (rate ratio 1.94, 95% confidence interval 1.40 to 2.69; p <0.001). In a model adjusted for study treatment arm, demographics, CVD risk factors, HIV characteristics, inflammatory markers, and other ECG abnormalities, a widened spatial QRS-T angle was associated with a >50% increased risk of CVD events compared to a normal spatial QRS-T angle (hazard ratio 1.53, 95% confidence interval 1.07 to 2.17; p = 0.02). No interaction was seen by SMART trial arm (p value for interaction = 0.37) or gender (p value for interaction = 0.84). In conclusion, a widened spatial QRS-T angle was independently predictive of CVD events in HIV-infected patients receiving antiretroviral therapy. This highlights the potential role of routine electrocardiography as a simple noninvasive CVD risk-screening tool in HIV-infected patients.
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Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel.
JAMA
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New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected adults in resource-rich settings.
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Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.
PLoS ONE
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Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96.
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Differences in lipid measurements by antiretroviral regimen exposure in cohorts from Asia and australia.
AIDS Res Treat
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We explored the mean differences in routinely measured lipids (total cholesterol, triglycerides, and high-density lipoprotein cholesterol) according to exposure to different combination antiretroviral regimens in Asian (n = 2051) and Australian (predominantly Caucasian, n = 794) cohorts. The regimen was defined as at least 3 antiretroviral drugs with at least 2 nucleoside-reverse transcriptases (NRTIs) and either of at least one protease inhibitor (PI) or non-nucleoside-reverse transcriptases (NNRTIs). We categorised cART regimens as: NRTIs as tenofovir based or not; NNRTIs as nevirapine or efavirenz (but not both); and PI as atazanavir based or not. We found that the impact of various antiretroviral regimens on lipids in Asian and Australian cohorts was only different by cohort for total cholesterol (P for interaction between regimen and cohort: <0.001) but not in case of other lipids (P for interaction: >0.05). The differences in total cholesterol were however small and unlikely to be of clinical significance. Overall, tenofovir with nevirapine or atazanavir was associated with the most favorable lipids, while the PI regimens without tenofovir and atazanavir were associated with least favorable lipids. We conclude that the impact of various ART regimens on lipids is largely similar in Asian and Australian cohorts and that the newer drugs such as tenofovir and atazanavir are likely to provide similar benefit in terms of lipid profiles in both populations.
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Non-cirrhotic portal hypertension in HIV mono-infected patients.
J. Gastroenterol. Hepatol.
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Unexplained liver injury including fibrosis and portal hypertension has rarely been reported among patients with HIV in the absence of co-infection with hepatitis B (HBV) or hepatitis C (HCV). We describe a series of HIV mono-infected patients with evidence of non-cirrhotic portal hypertension.
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Adherence to HIV treatment guidelines for comorbid disease assessment and initiation of antiretroviral therapy.
J. Acquir. Immune Defic. Syndr.
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There are limited data on adherence to HIV treatment guidelines. We assessed adherence to US Department of Health and Human Services guidelines with Australian Commentary for adults initiating antiretroviral therapy (ART).
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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.