142 results on '"Achhra, A"'
Search Results
2. Assessing Cardiovascular Risk in People Living with HIV: Current Tools and Limitations
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Achhra, Amit C., Lyass, Asya, Borowsky, Leila, Bogorodskaya, Milana, Plutzky, Jorge, Massaro, Joseph M., D’Agostino, Sr, Ralph B., and Triant, Virginia A.
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- 2021
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3. Acute Hepatitis due to Primary Human Immunodeficiency Virus Infection.
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Elliott, Eric I, Smith, Daisy, Lipscomb, Jonathan, Banini, Bubu, Meurer, Lindsay, Vanderford, Thomas H, Johnson, Jeffrey A, Jain, Dhanpat, and Achhra, Amit
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HIV infections ,PRIMARY immunodeficiency diseases ,HIV ,CHRONIC active hepatitis ,HEPATITIS - Abstract
The acute retroviral syndrome may present with diverse systemic manifestations and laboratory abnormalities. Here we present a rare case of primary human immunodeficiency virus (HIV) infection causing severe acute hepatitis. Liver histopathology demonstrated a pattern of lymphocytic inflammation consistent with acute hepatitis, high levels of HIV proviral DNA were detected within liver tissue, and immunofluorescence showed HIV p24 antigen within immune and parenchymal cells including hepatocytes. We review the literature pertaining to HIV infection of cell compartments within the liver and discuss the implications for HIV-associated acute liver disease. [ABSTRACT FROM AUTHOR]
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- 2024
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4. 1478. Evaluation Of Anal Cancer Screening Program in men who have sex with men (MSM) persons with HIV (PWH) At Two academic center HIV Clinics 2018-2022
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Achhra, Amit, primary, Chan, Elizabeth, additional, Applebaum, Serina, additional, Guerrero, Maggie, additional, Hao, Ritche, additional, Pantel, Haddon, additional, Virata, Michael D, additional, and Barakat, Lydia A, additional
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- 2023
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5. 1538. Is there value in performing yearly screening for latent tuberculosis infection by interferon-gamma release assay among patients living with HIV in non-endemic settings?
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Palacios, Carlo Foppiano, primary, Achhra, Amit, additional, Barakat, Lydia A, additional, Virata, Michael, additional, Hao, Richie, additional, Baxter, John D, additional, and Malinis, Maricar F, additional
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- 2023
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6. Factors associated with low HIV viral load
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Law, Achhra, A, Deeks, SG, Gazzard, B, Migueles, Novak, RM, Ristola, M, and Group, International Network for Strategic Initiatives in Global HIV Trials START Study
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Emerging Infectious Diseases ,Infectious Diseases ,Hepatitis - B ,Chronic Liver Disease and Cirrhosis ,Clinical Research ,Hepatitis - C ,Hepatitis ,HIV/AIDS ,Digestive Diseases ,Liver Disease ,Aetiology ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,2.2 Factors relating to the physical environment ,Infection ,Good Health and Well Being ,Adult ,Anti-Retroviral Agents ,Antiretroviral Therapy ,Highly Active ,CD4 Lymphocyte Count ,Cohort Studies ,Demography ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Time Factors ,Treatment Outcome ,Viral Load ,HIV ,antiretroviral therapy ,viral load ,International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) START Study Group ,Clinical Sciences ,Virology - Abstract
ObjectivesA small subset of HIV-positive adults have low HIV RNA in the absence of therapy, sometimes for years. Clinical factors associated with low HIV RNA in early infection have not been well defined.MethodsWe assessed factors associated with low plasma HIV RNA level at study entry in the Strategic Timing of AntiRetroviral Treatment (START) trial. All START participants had a baseline HIV RNA assessment within 60 days prior to randomization. The key covariables considered for this analysis were race, and hepatitis B virus (HBV) and hepatitis C virus (HCV) status. We assessed factors associated with HIV RNA ≤ 50 and ≤ 400 HIV-1 RNA copies/mL using logistic regression. Because of the strong association between region of randomization and baseline low HIV RNA, analyses were stratified by region.ResultsWe found that, of 4676 eligible participants randomized in START with a baseline HIV RNA assessment, 113 (2.4%) had HIV RNA ≤ 50 copies/mL at baseline, and a further 257 (5.5%) between 51 and 400 copies/mL. We found that HIV exposure routes other than male homosexual contact, higher high-density lipoprotein (HDL) cholesterol levels, higher CD4 cell counts, and higher CD4:CD8 ratio were associated with increased odds of low HIV RNA. HCV antibody positivity was borderline statistically significantly associated with low HIV RNA. Race and HBV surface antigen positivity were not significantly associated with low HIV RNA.ConclusionsIn a modern cohort of individuals with early untreated HIV infection, we found that HIV exposure routes other than male homosexual contact and higher HDL cholesterol were associated with increased odds of low HIV RNA.
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- 2015
7. Contrasting Cases of HIV Vasculopathy Associated Fusiform Aneurysms
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Kevin Kyle, Mary Maher, Amit C. Achhra, and Nagagopal Venna
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Neurology (clinical) - Abstract
Background Human Immunodeficiency Virus (HIV) vasculopathy encompasses the development of aneurysms, stenosis and vessel occlusions. Intracranial fusiform aneurysms in Human Immunodeficiency Virus (HIV) were originally described in children; however, HIV-associated aneurysms are increasingly recognized in adults. Purpose: We present two cases to highlight the spectrum of severity and outline instructive clinical courses. Results Case one is a 52-year-old woman with HIV, Acquired Immunodeficiency Syndrome (AIDS)-defining progressive multifocal leukoencephalopathy (PML) and an 18 years course of cerebral aneurysms, aneurysm thrombosis and the development of right middle cerebral artery (MCA) moyamoya pattern collaterals. Case two is a 55-year-old man with AIDS-defining cerebral toxoplasmosis, complicated by IRIS and anterior and posterior circulation fusiform aneurysm formation. Conclusions: The combination of both fusiform abnormalities and Moyamoya, discussed in our first case has not been previously described. In comparison, our second case actually demonstrated improvement in vasculopathy after nine-months of antiretroviral therapy (ART) adherence.
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- 2022
8. Weight-Based Data Center Selection Algorithm in Cloud Computing Environment
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Nandwani, Sunny, Achhra, Mohit, Shah, Raveena, Tamrakar, Aditi, Joshi, Kiran, Raksha, Sowmiya, Kacprzyk, Janusz, Series editor, Dash, Subhransu Sekhar, editor, Bhaskar, M. Arun, editor, Panigrahi, Bijaya Ketan, editor, and Das, Swagatam, editor
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- 2016
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9. Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial
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Achhra, Amit C., Mocroft, Amanda, Ross, Michael, Ryom-Nielson, Lene, Avihingsanon, Anchalee, Bakowska, Elzbieta, Belloso, Waldo, Clarke, Amanda, Furrer, Hansjakob, Lucas, Gregory M., Ristola, Matti, Rassool, Mohammed, Ross, Jonathan, Somboonwit, Charurut, Sharma, Shweta, and Wyatt, Christina
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- 2017
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10. Sex-based differences in antiretroviral therapy initiation, switching and treatment interruptions: global overview from the International Epidemiologic Databases to Evaluate AIDS (IeDEA)
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Giles, Michelle L, Achhra, Amit C, Abraham, Alison G, Haas, Andreas D, Gill, Michael John, Lee, Man Po, Luque, Marco, McGowan, Catherine, Cornell, Morna, Braitstein, Paula, de Rekeneire, Nathalie, Becquet, Renaud, Wools-Kaloustian, Kara, and Law, Matthew
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HIV infections -- Drug therapy -- Research ,Antiretroviral agents -- Dosage and administration ,Sex differences (Biology) -- Research ,Health - Abstract
Introduction: In 2015, the World Health Organization recommended that all HIV-infected individuals consider ART initiation as soon as possible after diagnosis. Sex differences in choice of initial ART regimen, indications for switching, time to switching and choice of second-line regimens have not been well described. The aims of this study were to describe first-line ART and CD4 count at ART initiation by sex, calendar year and region, and to analyse time to change or interruption in first-line ART, according to sex in each region. Methods: Participating cohorts included: Southern, East and West Africa (IeDEA-Africa), North America (NA-ACCORD), Caribbean, Central/South America (CCASAnet) and Asia-Pacific including Australia (IeDEA Asia-Pacific). The primary outcomes analysed for each region and according to sex were choice of initial ART, time to switching and time to discontinuation of the first-line regimen. Results and Discussion: The combined cohort data set comprised of 715,252 participants across seven regions from low- to high-income settings. The median CD4 count at treatment initiation was lower in men compared with women in nearly all regions and time periods. Women from North America and Southern Africa were more likely to switch ART compared to men (p < 0.001) with approximately 90% of women reporting a major change after 10 years in North America. Overall, after 8 years on ART, >50% of HIV- positive men and women from Southern Africa, East Africa, South and Central America remained on their original regimen. Men were more likely to have a treatment interruption compared with women in low- and middle-income countries from the Asia/Pacific region (p < 0.001) as were men from Southern Africa (p < 0.001). Greater than 75% of men and women did not report a treatment interruption after 10 years on ART from all regions except North America and Southern Africa. Conclusions: There are regional variations in the ART regimen commenced at baseline and rates of major change and treatment interruption according to sex. Some of this is likely to reflect changes in local and international antiretroviral guideline recommendations but other sex-specific factors such as pregnancy may contribute to these differences. Keywords: cohort studies; gender; treatment; women; sex; HIV, 1 | INTRODUCTION Over the past decade, HIV treatment guidelines have changed, with the CD[4.sup.+] count threshold for initiating antiretroviral therapy (ART) gradually increasing from less than 350 cells/[micro]L in [...]
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- 2018
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11. Efficacy and safety of contemporary dual-drug antiretroviral regimens as first-line treatment or as a simplification strategy: a systematic review and meta-analysis
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Achhra, Amit C, Mwasakifwa, Gwamaka, Amin, Janaki, and Boyd, Mark A
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- 2016
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12. Contrasting Cases of HIV Vasculopathy Associated Fusiform Aneurysms
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Kyle, Kevin, primary, Maher, Mary, additional, Achhra, Amit C., additional, and Venna, Nagagopal, additional
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- 2022
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13. Body Mass Index and the Risk of Serious Non-AIDS Events and All-Cause Mortality in Treated HIV-Positive Individuals: D: A: D Cohort Analysis
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Achhra, Amit C., Sabin, Caroline, Ryom, Lene, Hatleberg, Camilla, Antonella dʼAminio, Monforte, de Wit, Stephane, Phillips, Andrew, Pradier, Christian, Weber, Rainer, Reiss, Peter, El-Sadr, Wafaa, Bonnet, Fabrice, Mocroft, Amanda, Lundgren, Jens, and Law, Matthew G.
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- 2018
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14. Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV‐Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial
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Jason V. Baker, Shweta Sharma, Amit C. Achhra, Jose Ignacio Bernardino, Johannes R. Bogner, Daniel Duprez, Sean Emery, Brian Gazzard, Jonathan Gordin, Greg Grandits, Andrew N. Phillips, Siegfried Schwarze, Elsayed Z. Soliman, Stephen A. Spector, Giuseppe Tambussi, and Jens Lundgren
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antiretroviral therapy ,cholesterol ,HIV ,risk factor ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
IntroductionHIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. Methods and ResultsWe studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV‐positive persons with CD4+ cell counts >500 cells/mm3. Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV‐positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm3, an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low‐density lipoprotein cholesterol of 102 mg/dL, and high‐density lipoprotein cholesterol of 41 mg/dL. Mean follow‐up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow‐up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low‐density lipoprotein cholesterol and higher use of lipid‐lowering therapy (1.2%; 95% CI, 0.1–2.2). Concurrent increases in high‐density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high‐density lipoprotein cholesterol ratio (95% CI, 0.1–0.2). Immediate ART resulted in 2.3% less BP‐lowering therapy use (95% CI, 0.9–3.6), but there were no differences in new‐onset hypertension or diabetes mellitus. ConclusionsAmong HIV‐positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low‐density lipoprotein cholesterol but also concurrent increases in high‐density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant." Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00867048.
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- 2017
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15. Chronic Kidney Disease and Antiretroviral Therapy in HIV-Positive Individuals: Recent Developments
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Achhra, Amit C., Nugent, Melinda, Mocroft, Amanda, Ryom, Lene, and Wyatt, Christina M.
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- 2016
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16. Health Promotion in Australian General Practice: A Gap in GP Training
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Achhra, Amit
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- 2009
17. Assessing Cardiovascular Risk in People Living with HIV: Current Tools and Limitations
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Ralph B. D'Agostino, Amit C. Achhra, Milana Bogorodskaya, Jorge Plutzky, Leila H. Borowsky, Asya Lyass, Virginia A. Triant, and Joseph M. Massaro
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education.field_of_study ,Framingham Risk Score ,business.industry ,Population ,Human immunodeficiency virus (HIV) ,HIV Infections ,Disease ,medicine.disease_cause ,Risk Assessment ,Preventive care ,Article ,Infectious Diseases ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Risk Factors ,Virology ,Environmental health ,Coronary artery calcification ,Cohort ,medicine ,Humans ,Female ,education ,business ,Adverse effect - Abstract
PURPOSE OF REVIEW: To provide the current state of the development and application of cardiovascular disease (CVD) prediction tools in people living with HIV (PLWH). RECENT FINDINGS: Several risk prediction models developed on the general population are available to predict CVD risk, the most notable being the US-based pooled cohort equations (PCE), the Framingham risk functions, and the Europe-based SCORE (Systematic COronary Risk Evaluation). In validation studies in cohorts of PLWH, these models generally underestimate CVD risk, especially in individuals who are younger, women, Black race or predicted to be at low/intermediate risk. An HIV-specific CVD prediction model, the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) model, is available, but its performance is modest, especially in US-based cohorts. Enhancing CVD prediction with novel biomarkers of inflammation or coronary artery calcification is of interest but has not yet been evaluated in PLWH. Finally, studies on CVD risk prediction are lacking in diverse PLWH globally. SUMMARY: While available risk models for CVD prediction in PLWH remain suboptimal, clinicians should remain vigilant of higher CVD risk in this population and should use any of these risk scores for risk-stratification to guide preventive interventions. Focus on established traditional risk factors such as smoking remains critical in PLWH. Risk prediction functions tailored to PLWH in diverse settings will enhance clinicians’ ability to deliver optimal preventive care.
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- 2021
18. Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study*
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Achhra, A C, Mocroft, A, Reiss, P, Sabin, C, Ryom, L, de Wit, S, Smith, C J, Monforte, dʼArminio A, Phillips, A, Weber, R, Lundgren, J, and Law, M G
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- 2016
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19. Pre-therapy inflammation and coagulation activation and long-term CD4 count responses to the initiation of antiretroviral therapy*
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Achhra, A C, Phillips, A, Emery, S, MacArthur, R D, Furrer, H, De Wit, S, Losso, M, and Law, M G
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- 2015
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20. Plasma levels of cytokines and chemokines and the risk of mortality in HIV-infected individuals: a case–control analysis nested in a large clinical trial
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French, Martyn A., Cozzi-Lepri, Alessandro, Arduino, Roberto C., Johnson, Margaret, Achhra, Amit C., and Landay, Alan
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- 2015
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21. Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
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Achhra, AC, Mocroft, A, Ross, MJ, Ryom, L, Lucas, GM, Furrer, H, Neuhaus, J, Somboonwit, C, Kelly, M, Gatell, JM, and Wyatt, CM
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- 2015
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22. Clinical and demographic factors associated with low viral load in early untreated HIV infection in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
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Law, MG, Achhra, A, Deeks, SG, Gazzard, B, Migueles, SA, Novak, RM, and Ristola, M
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- 2015
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23. Baseline cardiovascular risk in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
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Soliman, EZ, Sharma, S, Arastéh, K, Wohl, D, Achhra, A, Tambussi, G, OʼConnor, J, Stein, JH, Duprez, DA, Neaton, JD, and Phillips, A
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- 2015
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24. Moving away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE)--agents that concern prescribers and patients: a feasibility study and call for a trial.
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Amit C Achhra, Mark A Boyd, Matthew G Law, Gail V Matthews, Anthony D Kelleher, and David A Cooper
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Medicine ,Science - Abstract
Regimens sparing RATE (ritonavir, abacavir, tenofovir, efavirienz) agents might have better long-term safety. We conducted a feasibility exercise to assess the potential for a randomised trial evaluating RATE-sparing regimens.Observational.We first calculated RATE-sparing options available to an average patient receiving RATE agents. We reviewed treatment history and all resistance assays from patients attending the St. Vincent's Hospital (Sydney) clinic and receiving ≥2 RATE agents (n = 120). A viable RATE-sparing regimen with 2 or 3 fully-active agents was constructed from the following six 'safer' agents: rilpivirine or etravirine; atazanavir; raltegravir; maraviroc; and lamivudine. Activity for each drug was predicted as 1 (full-activity), 0.5 or 0 (no activity) using the Stanford mutation database. The utility of maraviroc was calculated assuming both maraviroc activity and inactivity where unknown. The analysis was restricted to regimens for which supporting evidence was identified in the literature or conference proceedings. Finally, we calculated the proportion of patients in the nationally representative Australian HIV Observational Database (AHOD) cohort receiving ≥2 RATE agents (n = 1473) to measure the potential population-level uptake of RATE-sparing agents.Assuming full maraviroc activity, 117(97.5%) and 107(89.2%) individuals had at least one option with 2 or 3 active RATE-sparing agents, respectively. Assuming no maraviroc activity this decreased to 113(94.2%) and 104(86.7%), respectively. In AHOD, 837(56.8%) patients were receiving ≥2 RATE agents.Feasible treatment switch options sparing RATE agents exist for the majority of patients. Understanding the pros and cons of switching stable patients onto new RATE-sparing regimens requires evidence derived from randomised controlled trials.
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- 2014
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25. Digital Land Registry System Using Blockchain
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Richa Sharma, Nikita Achhra, Bhavesh Mangnani, Yugchhaya Galphat, Ekta Kithani, and Jaya Tanwani
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Intermediary ,Blockchain ,Land registration ,business.industry ,Currency ,Process (engineering) ,Cryptography ,business ,Computer security ,computer.software_genre ,Land tenure ,computer ,Hacker - Abstract
In today’s world, the security of data plays a very important role, many industrial sectors are trying to secure the data from hackers. Blockchain is an advanced technology through which peers can digitally transfer currency, financial documents, land properties, etc. It is an open-source public network where no central authority is needed, it is a peer-to-peer network where all transactions, value transfer, data shared through a single node would be verified by all other connected nodes in the network. The traditional land registration process is a slow and laborious process, involves many intermediaries, and has maximum chances of fraudulent and fake land transfer. Blockchain is a perfect domain for the land transfer process, in this paper proposed solution is given on securely transferring land ownership using blockchain technology, without involving any intermediaries, buyers and sellers are making a land ownership deal using ethereum network.
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- 2021
26. Digital Land Registry System Using Blockchain
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Sharma, Richa, primary, Galphat, Yugchhaya, additional, Kithani, Ekta, additional, Tanwani, Jaya, additional, Mangnani, Bhavesh, additional, and Achhra, Nikita, additional
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- 2021
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27. Differences in Lipid Measurements by Antiretroviral Regimen Exposure in Cohorts from Asia and Australia
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Amit C. Achhra, Janaki Amin, Jennifer Hoy, Junko Tanuma, Thira Sirisanthana, David Nolan, Tuti Merati, and Michelle Giles
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Immunologic diseases. Allergy ,RC581-607 - Abstract
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: 0.05). 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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- 2012
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28. Reclassification of risk of death with the knowledge of D-dimer in a cohort of treated HIV-infected individuals
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Achhra, Amit C., Amin, Janaki, Sabin, Caroline, Chu, Haitao, Dunn, David, Kuller, Lewis H., Kovacs, Joseph A., Cooper, David A., Emery, Sean, and Law, Matthew G.
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- 2012
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29. Race and CD4+ T-cell count in HIV prognosis and treatment
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Achhra, Amit C and Amin, Janaki
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- 2012
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30. Immunodeficiency and the risk of serious clinical endpoints in a well studied cohort of treated HIV-infected patients
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Achhra, Amit C, Amin, Janaki, Law, Matthew G, Emery, Sean, Gerstoft, Jan, Gordin, Fred M, Vjecha, Michael J, Neaton, James D, and Cooper, David A
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- 2010
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31. Body Mass Index and The Risk of Serious Non-Aids Events and All Cause Mortality in Treated Hiv-Positive Individuals: D: A: D Cohort Analysis
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Amanda Mocroft, Christian Pradier, Jens D Lundgren, Andrew N. Phillips, Lene Ryom, Amit C. Achhra, Camilla Ingrid Hatleberg, Monforte Antonella D'Aminio, Fabrice Bonnet, Peter Reiss, Caroline A. Sabin, Stéphane De Wit, Wafaa El-Sadr, Matthew Law, Rainer Weber, University of Zurich, Achhra, Amit C, AII - Infectious diseases, APH - Aging & Later Life, Global Health, and Infectious diseases
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Adult ,Male ,medicine.medical_specialty ,Population ,HIV Infections ,610 Medicine & health ,030204 cardiovascular system & hematology ,Body Mass Index ,Cohort Studies ,10234 Clinic for Infectious Diseases ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,Cause of Death ,Neoplasms ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,medicine ,Humans ,2736 Pharmacology (medical) ,Pharmacology (medical) ,Poisson Distribution ,030212 general & internal medicine ,Poisson regression ,education ,Cause of death ,2. Zero hunger ,education.field_of_study ,business.industry ,nutritional and metabolic diseases ,2725 Infectious Diseases ,Middle Aged ,medicine.disease ,3. Good health ,Infectious Diseases ,Cardiovascular Diseases ,Relative risk ,symbols ,Female ,business ,Body mass index ,Cohort study - Abstract
Background: The relationship between body mass index (BMI) [weight (kg)/height (m 2)] and serious non-AIDS events is not well understood. Methods: We followed D:A:D study participants on antiretroviral therapy from their first BMI measurement to the first occurrence of the endpoint or end of follow-up (N = 41,149 followed for 295,147 person-years). The endpoints were cardiovascular disease (CVD); diabetes; non-AIDS-defining cancers (NADCs) and BMI-NADCs (cancers known to be associated with BMI in general population); and all-cause mortality. Using Poisson regression models, we analyzed BMI as time-updated, lagged by 1 year, and categorized at: 18.5, 23, 25, 27.5, and 30 kg/m 2. Results: Participants were largely male (73%) with the mean age of 40 years (SD 9.7) and baseline median BMI of 23.3 (interquartile range: 21.2-25.7). Overall, BMI showed a statistically significant J-shaped relationship with the risk of all outcomes except diabetes. The relative risk (RR) for the BMI of 30 (95% confidence interval) compared with 23-25, respectively, was as follows: CVD: 1.46 (1.15-1.84) and 1.31 (1.03-1.67); NADCs: 1.78 (1.39-2.28) and 1.17 (0.88-1.54); and "BMI-NADCs": 1.29 (0.66-2.55) and 1.92 (1.10-3.36). For all-cause mortality, there was an interaction by sex (P < 0.001): RR in males: 2.47 (2.12-2.89) and 1.21 (0.97-1.50); and in females: 1.60 (1.30-1.98) and 1.02 (0.74-1.42). RR remained around 1 for intermediate categories of BMI. The risk of diabetes linearly increased with increasing BMI (P < 0.001). Conclusions: Risk of CVD, a range of cancers, and all-cause mortality increased at low BMI ( 30 with a relatively low risk at BMI of 23-25 and 25-30. High BMI was also associated with risk of diabetes.
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- 2018
32. Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: The D: A: D study
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Achhra, A. C, Mocroft, A., Reiss, P., Sabin, C., Ryom, L., de Wit, S., Smith, C. J., d'Arminio Monforte, A., Phillips, A., Weber, R., Lundgren, J., Law, M. G., Francisci, Daniela, Baldelli, Franco, Achhra, A. C., Mocroft, A., Reiss, P., Sabin, C., Ryom, L., De Wit, S., Smith, C. J., D'Arminio Monforte, A., Phillips, A., Weber, R., Lundgren, J., Law, M. G., on behalf of the D:a:d Study, Group, Castagna, A, The Kirby Institute for Infection and Immunity in Society (UNSW), University of New South Wales [Sydney] (UNSW), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Achhra, A, Mocroft, A, Reiss, P, Sabin, C, Ryom, L, de Wit, S, Smith, C, d'Arminio Monforte, A, Phillips, A, Weber, R, Lundgren, J, Law, M, and Gori, A
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Adult ,Male ,Anti-HIV Agents ,Infectious Disease ,HIV Infections ,Diabete ,NO ,Body Mass Index ,Cohort Studies ,Highly active antiretroviral therapy ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Risk Factors ,Body mass index ,Cardiovascular diseases ,Diabetes ,HIV ,Inflammation ,Myocardial infarction ,Weight gain ,Diabetes Mellitus ,Humans ,HIV Infection ,Pharmacology (medical) ,Obesity ,body mass index ,cardiovascular diseases ,diabetes ,highly active antiretroviral therapy ,inflammation ,myocardial infarction ,weight gain ,Risk Factor ,Health Policy ,Anti-HIV Agent ,Diabetes Mellitu ,Middle Aged ,Cardiovascular disease ,Infectious Diseases ,Cardiovascular Diseases ,Female ,Cohort Studie ,Human - Abstract
International audience; OBJECTIVES:The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of cardiovascular disease (CVD) and diabetes.METHODS:We analysed data from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre-ART) to 1 year after initiation (continuous variable) in treatment-naïve individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI [weight (kg)/(height (m))(2)] was categorized as underweight (< 18.5), normal (18.5-25), overweight (25-30) and obese (> 30). Poisson regression models were fitted stratified for each pre-ART BMI category to allow for category-specific estimates of incidence rate ratio (IRR). Models were adjusted for pre-ART BMI and CD4 count, key known risk factors (time-updated where possible) and calendar year.RESULTS:A total of 97 CVD events occurred in 43,982 person-years (n = 9321) and 125 diabetes events in 43,278 person-years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre-ART BMI category, was: underweight, 0.90 (0.60-1.37); normal, 1.18 (1.05-1.33); overweight, 0.87 (0.70-1.10), and obese, 0.95 (0.71-1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre-ART BMI (P for interaction > 0.05).CONCLUSIONS:Short-term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre-ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre-ART BMI.
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- 2016
33. Efficacy and safety of contemporary dual-drug antiretroviral regimens as first-line treatment or as a simplification strategy: a systematic review and meta-analysis
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Amit C. Achhra, Janaki Amin, Gwamaka Eliudi Mwasakifwa, and Mark A. Boyd
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Male ,Risk ,0301 basic medicine ,medicine.medical_specialty ,Anti-HIV Agents ,Epidemiology ,Immunology ,HIV Infections ,Pharmacology ,Maraviroc ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacotherapy ,Cyclohexanes ,Virology ,Internal medicine ,Odds Ratio ,medicine ,Humans ,030212 general & internal medicine ,Adverse effect ,business.industry ,Lamivudine ,Odds ratio ,Middle Aged ,Triazoles ,Viral Load ,030112 virology ,Infectious Diseases ,chemistry ,Meta-analysis ,Relative risk ,HIV-1 ,Reverse Transcriptase Inhibitors ,Drug Therapy, Combination ,business ,Viral load ,medicine.drug - Abstract
Summary Background Some guidelines recommended two-drug antiretroviral therapies as alternative regimens to triple therapy in selected patients with the aim of reducing drug burden and toxicity and preserving future treatment options. We aimed to assess the efficacy and safety of dual-therapy versus triple therapy as first-line treatment or in treatment simplification. Methods For this systematic review and meta-analysis, we searched Medline, Embase (via OVID), the Cochrane Trial Registry, and major conference proceedings for randomised trials published between Jan 1, 2008, and Dec 31, 2015. We included studies comparing dual-therapy (from two independent classes) antiretroviral regimens as a first-line or a switch strategy (in virologically suppressed individuals) with standard triple-drug regimens. Our primary outcome was the risk of virological failure (non-completion=failure) at the 48 week timepoint. We did a random-effect meta-analysis to pool the relative risk (RR) or odds ratio (OR) for each of the outcomes. Findings For the primary outcome, we included 21 studies (11 first-line and ten switch studies), providing data for 4821 individuals (2478 in dual-therapy groups and 2343 in control groups). Overall, the RR of failure with dual-therapy compared with triple-therapy (control) groups was 1·14 (95% CI 0·91–1·43). In first-line studies, the RR of failure for dual-therapy versus control groups was 1·17 (0·94–1·47; I 2 =51%), which reduced to 1·05 (0·86–1·28; I 2 =26%) on exclusion of maraviroc-containing studies. In switch studies, the RR of failure for dual-therapy versus control groups was 1·21 (0·72–2·02; I 2 =67%), which reduced to 1·13 (0·64–1·99; I 2 =61%) after exclusion of maraviroc-containing studies. In patients with a baseline viral load of more than 100 000 copies per mL, RR of failure for dual-therapy versus control groups was 1·24 (1·03–1·49), which reduced to 1·18 (0·94–1·47) on excluding maraviroc-containing studies. We recorded the ORs for dual-therapy versus control groups for serious adverse events (1·16 [0·92–1·48]), adverse events (0·82 [0·52–1·28]), and mutations (2·11 [1·32–3·36]). Interpretation Dual therapy, especially with regimens excluding maraviroc, could be safe and efficacious, particularly in patients with baseline viral loads of less than 100 000 copies per mL. However, dual therapy seems to have a greater risk of selecting resistance mutations compared with standard triple therapy. Funding None.
- Published
- 2016
34. Sex-based differences in antiretroviral therapy initiation, switching and treatment interruptions: global overview from the International Epidemiologic Databases to Evaluate AIDS (IeDEA)
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Matthew Law, Nathalie de Rekeneire, Andreas D Haas, Marco Tulio Luque, Paula Braitstein, Alison G. Abraham, Catherine C. McGowan, Kara Wools-Kaloustian, Michael Gill, Michelle L. Giles, Morna Cornell, Renaud Becquet, Man Po Lee, Amit C. Achhra, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Adult ,Male ,0301 basic medicine ,Time Factors ,Databases, Factual ,Anti-HIV Agents ,Human immunodeficiency virus (HIV) ,HIV Infections ,610 Medicine & health ,medicine.disease_cause ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Acquired immunodeficiency syndrome (AIDS) ,360 Social problems & social services ,gender ,medicine ,sex ,Humans ,030212 general & internal medicine ,Research Articles ,Sex Characteristics ,Pregnancy ,treatment ,business.industry ,Public Health, Environmental and Occupational Health ,HIV ,Guideline ,Middle Aged ,medicine.disease ,030112 virology ,CD4 Lymphocyte Count ,3. Good health ,Discontinuation ,Regimen ,Infectious Diseases ,Cohort ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,women ,business ,Research Article ,Cohort study ,Demography - Abstract
International audience; INTRODUCTION: In 2015, the World Health Organization recommended that all HIV-infected individuals consider ART initiation as soon as possible after diagnosis. Sex differences in choice of initial ART regimen, indications for switching, time to switching and choice of second-line regimens have not been well described. The aims of this study were to describe first-line ART and CD4 count at ART initiation by sex, calendar year and region, and to analyse time to change or interruption in first-line ART, according to sex in each region. METHODS: Participating cohorts included: Southern, East and West Africa (IeDEA-Africa), North America (NA-ACCORD), Caribbean, Central/South America (CCASAnet) and Asia-Pacific including Australia (IeDEA Asia-Pacific). The primary outcomes analysed for each region and according to sex were choice of initial ART, time to switching and time to discontinuation of the first-line regimen. RESULTS AND DISCUSSION: The combined cohort data set comprised of 715,252 participants across seven regions from low- to high-income settings. The median CD4 count at treatment initiation was lower in men compared with women in nearly all regions and time periods. Women from North America and Southern Africa were more likely to switch ART compared to men (p < 0.001) with approximately 90% of women reporting a major change after 10 years in North America. Overall, after 8 years on ART, >50% of HIV- positive men and women from Southern Africa, East Africa, South and Central America remained on their original regimen. Men were more likely to have a treatment interruption compared with women in low- and middle-income countries from the Asia/Pacific region (p < 0.001) as were men from Southern Africa (p < 0.001). Greater than 75% of men and women did not report a treatment interruption after 10 years on ART from all regions except North America and Southern Africa. CONCLUSIONS: There are regional variations in the ART regimen commenced at baseline and rates of major change and treatment interruption according to sex. Some of this is likely to reflect changes in local and international antiretroviral guideline recommendations but other sex-specific factors such as pregnancy may contribute to these differences.
- Published
- 2018
35. Pre-therapy inflammation and coagulation activation and long-term CD4 count responses to the initiation of antiretroviral therapy
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Hansjakob Furrer, S De Wit, Matthew Law, Amit C. Achhra, M. H. Losso, Sean Emery, Andrew N. Phillips, and Rodger D. MacArthur
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medicine.medical_specialty ,Randomization ,biology ,business.industry ,Health Policy ,C-reactive protein ,Retrospective cohort study ,law.invention ,Infectious Diseases ,Quartile ,Randomized controlled trial ,law ,Interquartile range ,Internal medicine ,Cohort ,Immunology ,biology.protein ,medicine ,Biomarker (medicine) ,Pharmacology (medical) ,business - Abstract
OBJECTIVES Pre-antiretroviral therapy (ART) inflammation and coagulation activation predict clinical outcomes in HIV-positive individuals. We assessed whether pre-ART inflammatory marker levels predicted the CD4 count response to ART. METHODS Analyses were based on data from the Strategic Management of Antiretroviral Therapy (SMART) trial, an international trial evaluating continuous vs. interrupted ART, and the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial, evaluating three first-line ART regimens with at least two drug classes. For this analysis, participants had to be ART-naive or off ART at randomization and (re)starting ART and have C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer measured pre-ART. Using random effects linear models, we assessed the association between each of the biomarker levels, categorized as quartiles, and change in CD4 count from ART initiation to 24 months post-ART. Analyses adjusted for CD4 count at ART initiation (baseline), study arm, follow-up time and other known confounders. RESULTS Overall, 1084 individuals [659 from SMART (26% ART naive) and 425 from FIRST] met the eligibility criteria, providing 8264 CD4 count measurements. Seventy-five per cent of individuals were male with the mean age of 42 years. The median (interquartile range) baseline CD4 counts were 416 (350-530) and 100 (22-300) cells/μL in SMART and FIRST, respectively. All of the biomarkers were inversely associated with baseline CD4 count in FIRST but not in SMART. In adjusted models, there was no clear relationship between changing biomarker levels and mean change in CD4 count post-ART (P for trend: CRP, P = 0.97; IL-6, P = 0.25; and D-dimer, P = 0.29). CONCLUSIONS Pre-ART inflammation and coagulation activation do not predict CD4 count response to ART and appear to influence the risk of clinical outcomes through other mechanisms than blunting long-term CD4 count gain.
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- 2015
36. Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
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Mj Ross, Gm Lucas, Amanda Mocroft, Cm Wyatt, Lene Ryom, Hansjakob Furrer, Jacqueline Neuhaus, Ac Achhra, M Kelly, Jm Gatell, and Charurut Somboonwit
- Subjects
medicine.medical_specialty ,Creatinine ,education.field_of_study ,Proteinuria ,business.industry ,Cross-sectional study ,Health Policy ,Population ,Renal function ,Odds ratio ,urologic and male genital diseases ,medicine.disease ,female genital diseases and pregnancy complications ,chemistry.chemical_compound ,Infectious Diseases ,chemistry ,Internal medicine ,Cohort ,medicine ,Pharmacology (medical) ,medicine.symptom ,Intensive care medicine ,business ,education ,Kidney disease - Abstract
Objectives HIV infection has been associated with an increased risk of chronic kidney disease (CKD). Little is known about the prevalence of CKD in individuals with high CD4 cell counts prior to initiation of antiretroviral therapy (ART). We sought to address this knowledge gap. Methods We describe the prevalence of CKD among 4637 ART-naive adults (mean age 36.8 years) with CD4 cell counts > 500 cells/μL at enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. CKD was defined by estimated glomerular filtration rate (eGFR) 500 cells/μL.
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- 2015
37. Clinical and demographic factors associated with low viral load in early untreated HIV infection in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
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Steven G. Deeks, Matthew Law, Matti Ristola, Brian Gazzard, Richard M. Novak, Stephen A. Migueles, and Amit C. Achhra
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business.industry ,Health Policy ,Treatment outcome ,Human immunodeficiency virus (HIV) ,virus diseases ,medicine.disease_cause ,Antiretroviral therapy ,Infectious Diseases ,Immunology ,medicine ,Antiretroviral treatment ,Pharmacology (medical) ,business ,Viral load ,Cohort study - Abstract
Objectives A small subset of HIV-positive adults have low HIV RNA in the absence of therapy, sometimes for years. Clinical factors associated with low HIV RNA in early infection have not been well defined.
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- 2015
38. Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV‐Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial
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Shweta Sharma, Stephen A. Spector, Andrew N. Phillips, Jens D Lundgren, Daniel A. Duprez, Jose I Bernardino, Johannes R. Bogner, Jonathan S. Gordin, Elsayed Z. Soliman, Amit C. Achhra, Giuseppe Tambussi, Greg Grandits, Brian Gazzard, Jason V. Baker, Siegfried Schwarze, and Sean Emery
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Male ,Time Factors ,Human immunodeficiency virus (HIV) ,HIV Infections ,Comorbidity ,Disease ,030204 cardiovascular system & hematology ,Global Health ,medicine.disease_cause ,Anti-HIV Agents/administration & dosage ,0302 clinical medicine ,Comorbidity/trends ,Risk Factors ,Cardiovascular Disease ,Global health ,030212 general & internal medicine ,Preventive Cardiology ,Original Research ,Lipids and Cholesterol ,3. Good health ,risk factor ,Cardiovascular Diseases ,Female ,Cardiology and Cardiovascular Medicine ,Risk assessment ,Mercaptoethanol/analogs & derivatives ,Adult ,medicine.medical_specialty ,Anti-HIV Agents ,antiretroviral therapy ,HIV Infections/drug therapy ,Risk Assessment ,Drug Administration Schedule ,Cyclic N-Oxides ,03 medical and health sciences ,Internal medicine ,medicine ,Antiretroviral treatment ,Humans ,Risk factor ,Mercaptoethanol ,business.industry ,Cardiovascular Diseases/epidemiology ,HIV ,cholesterol ,medicine.disease ,Antiretroviral therapy ,Immunology ,business ,Follow-Up Studies - Abstract
Introduction HIV infection and certain antiretroviral therapy ( ART ) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. Methods and Results We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV‐positive persons with CD 4 + cell counts >500 cells/mm 3 . Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV ‐positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm 3 , an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low‐density lipoprotein cholesterol of 102 mg/dL, and high‐density lipoprotein cholesterol of 41 mg/dL. Mean follow‐up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow‐up time taking ART , respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low‐density lipoprotein cholesterol and higher use of lipid‐lowering therapy (1.2%; 95% CI , 0.1–2.2). Concurrent increases in high‐density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high‐density lipoprotein cholesterol ratio (95% CI , 0.1–0.2). Immediate ART resulted in 2.3% less BP ‐lowering therapy use (95% CI , 0.9–3.6), but there were no differences in new‐onset hypertension or diabetes mellitus. Conclusions Among HIV‐positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low‐density lipoprotein cholesterol but also concurrent increases in high‐density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant." Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00867048.
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- 2017
39. Development and Evaluation of Sucrose Free Herbal Orally Disintegrating Tablets of Ginger
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Achhra Cv and Pawar Ha
- Subjects
Sucrose ,Aspartame ,biology ,Gram-positive bacteria ,Pharmaceutical Science ,02 engineering and technology ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Antimicrobial ,Sugar free ,chemistry.chemical_compound ,Granulation ,020303 mechanical engineering & transports ,0203 mechanical engineering ,chemistry ,In vivo ,medicine ,Mannitol ,Food science ,0210 nano-technology ,medicine.drug - Abstract
The objective of the present study was to develop orally disintegrating tablets of dry ginger powder with sugar free ingredients. In the present research work, orally disintegrating tablets of ginger were prepared by wet granulation method. A total of eight formulations were prepared with different compositions. The formulated tablets were evaluated for post-compression parameters. FTIR spectroscopic studies revealed that there was no interaction between the dry ginger powder and other excipients used in the formulations. The disintegration time of the optimized formulation was less than 30 sec. The in vitro release study of optimized formulation showed more than 90% drug release at the end of 10 min. The optimized formulation B8 showed good in vitro and in vivo antimicrobial activity against Gram positive bacteria Staphylococcus aureus, Corynebacterium diphtheriae, Streptococcus pyogenes and Gram-negative bacteria Klebsiella pneumoniae. The formulation B8 was found to be stable for one month under accelerated stability condition.
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- 2017
40. Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial
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Michael W. Ross, Charurut Somboonwit, Waldo H. Belloso, Mohammed Rassool, Lene Ryom-Nielson, Amit C. Achhra, Elzbieta Bakowska, Gregory M. Lucas, Anchalee Avihingsanon, Matti Ristola, Jonathan D C Ross, Amanda Clarke, Amanda Mocroft, Hansjakob Furrer, Shweta Sharma, Christina M. Wyatt, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, and HUS Inflammation Center
- Subjects
CHRONIC KIDNEY-DISEASE ,0301 basic medicine ,Male ,HAART ,HIV Infections ,Urine ,VARIANTS ,Kidney ,chemistry.chemical_compound ,0302 clinical medicine ,Antiretroviral Therapy, Highly Active ,eGFR ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Longitudinal Studies ,1183 Plant biology, microbiology, virology ,RISK ,INFECTED PATIENTS ,IMMUNODEFICIENCY ,Proteinuria ,Cobicistat ,ASSOCIATION ,General Medicine ,Middle Aged ,Infectious Diseases ,Anti-Retroviral Agents ,317 Pharmacy ,Female ,medicine.symptom ,Glomerular Filtration Rate ,Microbiology (medical) ,Adult ,medicine.medical_specialty ,NEPHROPATHY ,Renal function ,Lower risk ,Article ,Nephropathy ,03 medical and health sciences ,Internal medicine ,CKD ,Humans ,AIDS-Associated Nephropathy ,Aged ,Creatinine ,SERUM CREATININE ,business.industry ,HIV ,medicine.disease ,030112 virology ,Surgery ,COBICISTAT ,Regimen ,chemistry ,3121 General medicine, internal medicine and other clinical medicine ,TENOFOVIR ,business ,START - Abstract
The impact of early ART initiation (versus deferring) on kidney function has not been studied. START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4 + (cells/mm 3 ) counts >500. Serum creatinine and urine dipstick protein were measured at Months 0, 1, 4, 8 and 12, and annually thereafter. The two arms were compared for changes in eGFR (mL/min/1.73 m 2 , calculated by CKD-EPI equation), over time using longitudinal mixed models. Of 4685 START participants, 4629 (2294 in immediate and 2335 deferred arm) were included. Median baseline CD4 + and eGFR were 651 and 111.5, respectively. ART was initiated in 2271 participants (99.0%) in the immediate and 1127 (48.3%) in the deferred arm, accounting for >94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 0.56 (95% CI 0.003–1.11) higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or bPI use (1.85, 95% CI 1.21–2.50) and in Black participants (30.1% overall) (3.90, 95% CI 2.84–4.97) versus non-Blacks (1.05, 95% CI 0.33–1.77) ( P P = 0.049). In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower proteinuria risk versus deferring ART (more pronounced in Black participants). Whether this early benefit translates into a lower risk of CKD requires further follow-up.
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- 2016
41. Changes in Metabolic, Inflammatory and Coagulation Biomarkers after HIV Seroconversion – the Health in Men (Him) Biomarker Substudy
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Julie Yeung, David A. Cooper, Janaki Amin, Anthony D. Kelleher, Amit C. Achhra, Matthew Law, and Andrew E. Grulich
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Adult ,Male ,Vitamin ,medicine.medical_specialty ,Population ,Fibrinogen ,chemistry.chemical_compound ,High-density lipoprotein ,Risk Factors ,Internal medicine ,HIV Seropositivity ,medicine ,Vitamin D and neurology ,Humans ,Pharmacology (medical) ,Seroconversion ,education ,Blood Coagulation ,Inflammation ,Pharmacology ,education.field_of_study ,business.industry ,Case-control study ,Infectious Diseases ,chemistry ,Case-Control Studies ,Biomarker (medicine) ,business ,Biomarkers ,medicine.drug - Abstract
Background Biomarkers of inflammation, coagulation, lipids and vitamin D have been associated with cardiovascular and mortality risk in HIV-infected individuals. Scarce data exist on changes in these markers from pre-to post-HIV seroconversion. Methods The study participants were drawn from the Health in Men Study, which recruited HIV-negative homosexual men. Participants with incident HIV infection ( n=26) were compared with HIV-negative controls ( n=52) matched on age at enrolment, date of visit and reported intravenous drug use. Levels of metabolic (lipids and vitamin D), inflammatory (C-reactive protein and interleukin-6) and coagulation (D-dimer and fibrinogen) biomarkers were measured at pre- and post-HIV seroconversion visits and corresponding visits for controls. Random-effect models were used to compare changes in markers between cases and controls. Results The median gap between pre- and post-seroconversion or matched first and second visits in controls was 12 months. HIV seroconversion was associated with decline in high density lipoprotein (HDL-C; difference in mean change between cases and controls -0.14 mmol/l; 95% CI -0.22, -0.01; P=0.035). There were no significant differences in changes in other lipids, markers of inflammation, coagulation or vitamin D. Conclusions Decline in HDL-C seems to be the main proatherogenic change within 1–1.5 years after HIV seroconversion. HIV seroconversion was not associated with profound changes in other lipids, or markers of inflammation, coagulation and vitamin D. Longitudinal assessment of these markers in comparable population needs further assessment.
- Published
- 2013
42. Chronic Kidney Disease and Antiretroviral Therapy in HIV-Positive Individuals: Recent Developments
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Amit C. Achhra, Melinda M. Nugent, Amanda Mocroft, Lene Ryom, and Christina M. Wyatt
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Anti-HIV Agents ,Population ,Renal function ,HIV Infections ,urologic and male genital diseases ,Lower risk ,Tenofovir alafenamide ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Virology ,Internal medicine ,Diabetes mellitus ,Antiretroviral Therapy, Highly Active ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Longitudinal Studies ,Prospective Studies ,Renal Insufficiency, Chronic ,education ,Intensive care medicine ,Tenofovir ,education.field_of_study ,Framingham Risk Score ,business.industry ,Adenine ,HIV Protease Inhibitors ,medicine.disease ,030112 virology ,Discontinuation ,Infectious Diseases ,business ,Kidney disease ,Glomerular Filtration Rate - Abstract
Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted protease inhibitors (PI/rs), have been associated with increased risk of CKD. However, the CKD risk attributable to these agents is overall small, especially in those with low baseline risk of CKD and normal renal function. CKD risk in HIV-positive individuals can be further minimized by timely identification of those with worsening renal function and discontinuation of potentially nephrotoxic agents. Clinicians can use several monitoring tools, including the D:A:D risk score and routine measurements of estimated glomerular filtration (eGFR) and proteinuria, to identify high-risk individuals who may require an intervention. Tenofovir alafenamide (TAF), a TDF alternative, promises to be safer in terms of TDF-associated kidney and bone toxicity. While the short-term data on TAF does indicate lower eGFR decline and lower risk of proteinuria (vs. TDF), long-term data on renal safety of TAF are still awaited. Promising results have also emerged from recent trials on alternative dual-therapy antiretroviral regimens which exclude the nucleoside(tide) reverse transcriptase class as well as possibly the PI/rs, thereby reducing the drug burden, and possibly the toxicity. However, long-term safety or benefits of these dual-therapy regimens are still unclear and will need to be studied in future prospective studies. Finally, addressing risk factors such as hypertension and diabetes will continue to be important in this population.
- Published
- 2016
43. Weight-Based Data Center Selection Algorithm in Cloud Computing Environment
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Mohit Achhra, Sowmiya Raksha, Aditi Tamrakar, Raveena Shah, Sunny Nandwani, and K. K. Joshi
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Service (systems architecture) ,Computer science ,business.industry ,Cloud computing ,Provisioning ,computer.software_genre ,Virtual machine ,Scalability ,Data center ,The Internet ,business ,computer ,Selection algorithm ,Computer network - Abstract
Cloud computing is Internet-based computing, whereby shared and distributed resources and information are provided on demand. It involves provision of dynamically scalable and virtualized resources. Perhaps, with such high provisioning of scalability and on-demand resource availability and high computational facilities, cloud also faces many issues. Service availability on demand, unpredictability of performance, on-time availability of resources, data confidentiality, security, and privacy are the major challenges in cloud computing e. Different simulation tools are available to analyze and test the execution of algorithm. CloudAnalyst is one of the simulation tools used to model and analyze cloud computing environment before the actual deployment. Cloud Application Service Broker determines which data center should service the request from each user base. Service proximity-based routing selects the data center which has lowest network latency or minimum transmission delay from a user base. If there are more than one data centers in a region in close proximity, then one of the data centers is selected at random to service the incoming request. However, other factors such as cost, workload, number of virtual machines, processing time etc., are not taken into consideration. Randomly selected data center gives undesirable results in terms of response time, data processing time, cost, and other parameters. In this paper, we propose a weight-based data center selection algorithm which proves to improvise the randomized service proximity-based routing in terms of processing time, i.e., performance and costs.
- Published
- 2016
44. Development and Evaluation of Sucrose Free Herbal Orally Disintegrating Tablets of Ginger
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CV, Achhra, primary and HA, Pawar, additional
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- 2017
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45. Baseline cardiovascular risk in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
- Author
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E Z, Soliman, S, Sharma, K, Arastéh, D, Wohl, A, Achhra, G, Tambussi, J, O'Connor, J H, Stein, D A, Duprez, J D, Neaton, and A, Phillips
- Subjects
Adult ,Male ,Electrocardiography ,Cross-Sectional Studies ,Cardiovascular Diseases ,Prevalence ,Humans ,Female ,HIV Infections ,Middle Aged ,Risk Assessment ,Article ,CD4 Lymphocyte Count - Abstract
The Strategic Timing of AntiRetroviral Treatment (START) trial has recruited antiretroviral-naïve individuals with high CD4 cell counts from all regions of the world. We describe the distribution of cardiovascular disease (CVD) risk factors, overall and by geographical region, at study baseline.The distribution of CVD risk factors was assessed and compared by geographical region among START participants who had a baseline electrocardiogram (n = 4019; North America, 11%; Europe/Australia/Israel, 36%; South America, 26%; Asia, 4%; Africa, 23%; median age 36 years; 26% female).About 58.3% (n = 2344) of the participants had at least one CVD risk factor and 18.9% (n = 761) had two or more. The most common CVD risk factors were current smoking (32%), hypertension (19.3%) and obesity (16.5%). There were significant differences in the prevalence of CVD risk factors among geographical regions. The prevalence of at least one risk factor across regions was as follows: North America, 70.0%; Europe/Australia/Israel, 65.1%; South America, 49.4%; Asia, 37.0%; Africa, 55.8% (P-value 0.001). Significant regional differences were also observed when risk factors were used as part of the Framingham and Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) risk scores or used to define a favourable risk profile.CVD risk factors are common among START participants, and their distribution varies by geographical region. Better understanding of how and why CVD risk factors develop in people with HIV infection and their geographical distributions could shed light on appropriate strategies for CVD prevention and may inform the interpretation of the results of START, as CVD is expected to be a major fraction of the primary endpoints observed.
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- 2015
46. Plasma levels of cytokines and chemokines and the risk of mortality in HIV-infected individuals: a case-control analysis nested in a large clinical trial
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Martyn A. French, Alessandro Cozzi-Lepri, Roberto C. Arduino, Amit C. Achhra, Margaret A. Johnson, and Alan L. Landay
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Male ,Chemokine ,medicine.medical_treatment ,Immunology ,Inflammation ,HIV Infections ,Biology ,Risk Assessment ,Article ,Proinflammatory cytokine ,medicine ,Risk of mortality ,Immunology and Allergy ,Humans ,Survival analysis ,Clinical Trials as Topic ,Case-control study ,Prognosis ,Survival Analysis ,Infectious Diseases ,Cytokine ,Case-Control Studies ,biology.protein ,Cytokines ,Female ,medicine.symptom ,Cell activation ,Biomarkers - Abstract
BACKGROUND All-cause mortality and serious non-AIDS events (SNAEs) in individuals with HIV-1 infection receiving antiretroviral therapy are associated with increased production of interleukin-6 which appears to be driven by monocyte/macrophage activation. Plasma levels of other cytokines or chemokines associated with immune activation might also be biomarkers of an increased risk of mortality and/or SNAEs. METHODS Baseline plasma samples from 142 participants enrolled into the Strategies for Management of Antiretroviral Therapy study, who subsequently died, and 284 matched controls, were assayed for levels of 15 cytokines and chemokines. Cytokine and chemokine levels were analysed individually and when grouped according to function (innate/proinflammatory response, cell trafficking and cell activation/proliferation) for their association with the risk of subsequent death. RESULTS Higher plasma levels of proinflammatory cytokines (interleukin-6 and tumour necrosis factor-α) were associated with an increased risk of all-cause mortality but in analyses adjusted for potential confounders, only the association with interleukin-6 persisted. Increased plasma levels of the chemokine CXCL8 were also associated with all-cause mortality independently of hepatitis C virus status but not when analyses were adjusted for all confounders. In contrast, higher plasma levels of cytokines mediating cell activation/proliferation were not associated with a higher mortality risk and exhibited a weak protective effect when analysed as a group. CONCLUSION Whereas plasma levels of interleukin-6 are the most informative biomarker of cytokine dysregulation associated with all-cause mortality in individuals with HIV-1 infection, assessment of plasma levels of CXCL8 might provide information about causes of mortality and possibly SNAEs.
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- 2015
47. Pre-therapy inflammation and coagulation activation and long-term CD4 count responses to the initiation of antiretroviral therapy
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A C, Achhra, A, Phillips, S, Emery, R D, MacArthur, H, Furrer, S, De Wit, M, Losso, and M G, Law
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Adult ,Inflammation ,Male ,Anti-HIV Agents ,Interleukin-6 ,HIV Infections ,Article ,CD4 Lymphocyte Count ,Fibrin Fibrinogen Degradation Products ,C-Reactive Protein ,Predictive Value of Tests ,Risk Factors ,Disease Progression ,Humans ,Female ,Blood Coagulation ,Biomarkers ,Retrospective Studies - Abstract
Pre-antiretroviral therapy (ART) inflammation and coagulation activation predict clinical outcomes in HIV-positive individuals. We assessed whether pre-ART inflammatory marker levels predicted the CD4 count response to ART.Analyses were based on data from the Strategic Management of Antiretroviral Therapy (SMART) trial, an international trial evaluating continuous vs. interrupted ART, and the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial, evaluating three first-line ART regimens with at least two drug classes. For this analysis, participants had to be ART-naïve or off ART at randomization and (re)starting ART and have C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer measured pre-ART. Using random effects linear models, we assessed the association between each of the biomarker levels, categorized as quartiles, and change in CD4 count from ART initiation to 24 months post-ART. Analyses adjusted for CD4 count at ART initiation (baseline), study arm, follow-up time and other known confounders.Overall, 1084 individuals [659 from SMART (26% ART naïve) and 425 from FIRST] met the eligibility criteria, providing 8264 CD4 count measurements. Seventy-five per cent of individuals were male with the mean age of 42 years. The median (interquartile range) baseline CD4 counts were 416 (350-530) and 100 (22-300) cells/μL in SMART and FIRST, respectively. All of the biomarkers were inversely associated with baseline CD4 count in FIRST but not in SMART. In adjusted models, there was no clear relationship between changing biomarker levels and mean change in CD4 count post-ART (P for trend: CRP, P = 0.97; IL-6, P = 0.25; and D-dimer, P = 0.29).Pre-ART inflammation and coagulation activation do not predict CD4 count response to ART and appear to influence the risk of clinical outcomes through other mechanisms than blunting long-term CD4 count gain.
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- 2015
48. Baseline cardiovascular risk in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial: Baseline CVD in START
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Elsayed Z. Soliman, James H. Stein, Andrew N. Phillips, Jemma L O'Connor, James D. Neaton, Keikawus Arastéh, Amit C. Achhra, Daniel A. Duprez, David A. Wohl, Giuseppe Tambussi, and Shweta Sharma
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medicine.medical_specialty ,business.industry ,Health Policy ,Human immunodeficiency virus (HIV) ,medicine.disease_cause ,Coronary heart disease ,Infectious Diseases ,Emergency medicine ,medicine ,Physical therapy ,Geographic regions ,Antiretroviral treatment ,Pharmacology (medical) ,Cd4 cell count ,Baseline (configuration management) ,business ,Hiv disease - Abstract
Introduction The Strategic Timing of AntiRetroviral Treatment (START) trial has recruited antiretroviral-naive individuals with high CD4 cell counts from all world regions. We describe the distribution of cardiovascular (CVD) risk factors, overall and by geographic region, at study baseline.
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- 2015
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49. Clinical and demographic factors associated with low viral load in early untreated HIV infection in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
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M G, Law, A, Achhra, S G, Deeks, B, Gazzard, S A, Migueles, R M, Novak, and M, Ristola
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Adult ,Male ,Time Factors ,HIV Infections ,Middle Aged ,Viral Load ,Article ,CD4 Lymphocyte Count ,Cohort Studies ,Treatment Outcome ,Anti-Retroviral Agents ,Antiretroviral Therapy, Highly Active ,Humans ,Female ,Demography - Abstract
A small subset of HIV-positive adults have low HIV RNA in the absence of therapy, sometimes for years. Clinical factors associated with low HIV RNA in early infection have not been well defined.We assessed factors associated with low plasma HIV RNA level at study entry in the Strategic Timing of AntiRetroviral Treatment (START) trial. All START participants had a baseline HIV RNA assessment within 60 days prior to randomization. The key covariables considered for this analysis were race, and hepatitis B virus (HBV) and hepatitis C virus (HCV) status. We assessed factors associated with HIV RNA ≤ 50 and ≤ 400 HIV-1 RNA copies/mL using logistic regression. Because of the strong association between region of randomization and baseline low HIV RNA, analyses were stratified by region.We found that, of 4676 eligible participants randomized in START with a baseline HIV RNA assessment, 113 (2.4%) had HIV RNA ≤ 50 copies/mL at baseline, and a further 257 (5.5%) between 51 and 400 copies/mL. We found that HIV exposure routes other than male homosexual contact, higher high-density lipoprotein (HDL) cholesterol levels, higher CD4 cell counts, and higher CD4:CD8 ratio were associated with increased odds of low HIV RNA. HCV antibody positivity was borderline statistically significantly associated with low HIV RNA. Race and HBV surface antigen positivity were not significantly associated with low HIV RNA.In a modern cohort of individuals with early untreated HIV infection, we found that HIV exposure routes other than male homosexual contact and higher HDL cholesterol were associated with increased odds of low HIV RNA.
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- 2014
50. Kidney disease in antiretroviral-naïve HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial
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A C, Achhra, A, Mocroft, M J, Ross, L, Ryom, G M, Lucas, H, Furrer, J, Neuhaus, C, Somboonwit, M, Kelly, J M, Gatell, and C M, Wyatt
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Adult ,Male ,HIV Infections ,Middle Aged ,Article ,CD4 Lymphocyte Count ,Cross-Sectional Studies ,Risk Factors ,Chronic Disease ,Prevalence ,Humans ,Female ,Kidney Diseases ,Glomerular Filtration Rate - Abstract
HIV infection has been associated with an increased risk of chronic kidney disease (CKD). Little is known about the prevalence of CKD in individuals with high CD4 cell counts prior to initiation of antiretroviral therapy (ART). We sought to address this knowledge gap.We describe the prevalence of CKD among 4637 ART-naïve adults (mean age 36.8 years) with CD4 cell counts 500 cells/μL at enrolment in the Strategic Timing of AntiRetroviral Treatment (START) study. CKD was defined by estimated glomerular filtration rate (eGFR) 60 mL/min/1.73 m(2) and/or dipstick urine protein ≥ 1+. Logistic regression was used to identify baseline characteristics associated with CKD.Among 286 [6.2%; 95% confidence interval (CI) 5.5%, 6.9%] participants with CKD, the majority had isolated proteinuria. A total of 268 participants had urine protein ≥ 1+, including 41 with urine protein ≥ 2+. Only 22 participants (0.5%) had an estimated glomerular filtration rate 60 mL/min/1.73 m(2) , including four who also had proteinuria. Baseline characteristics independently associated with CKD included diabetes [adjusted odds ratio (aOR) 1.73; 95% CI 1.05, 2.85], hypertension (aOR 1.82; 95% CI 1.38, 2.38), and race/ethnicity (aOR 0.59; 95% CI 0.37, 0.93 for Hispanic vs. white).We observed a low prevalence of CKD associated with traditional CKD risk factors among ART-naïve clinical trial participants with CD4 cell counts 500 cells/μL.
- Published
- 2014
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