44 results on '"Gharakhanian S"'
Search Results
2. Metabolic disorders and chronic viral disease: The case of HIV and HCV
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Slama, L., Le Camus, C., Serfaty, L., Pialoux, G., Capeau, J., and Gharakhanian, S.
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- 2009
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3. « L'observance thérapeutique au cours de l'infection VIH, une approche multidisciplinaire »
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Slama, L., Le Camus, C., Amiel, C., Pialoux, G., and Gharakhanian, S.
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- 2006
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4. Documented rapid course of hepatic fibrosis between two biopsies in patients coinfected by HIV and HCV despite high CD4 cell count
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Bonnard, P., Lescure, F. X., Amiel, C., Guiard-Schmid, J.-B., Callard, P., Gharakhanian, S., and Pialoux, Gilles
- Published
- 2007
5. Differences in androgens of HIV positive patients with and without Kaposi sarcoma
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Christeff, N., Winter, C., Gharakhanian, S., Thobie, N., Wirbel, E., Costagliola, D., Nunez, E. A., and Rozenbaum, W.
- Published
- 1995
6. T-07: VAC-3S, un nouveau vaccin immunothérapeutique de l’infection VIH-1 : résultats de la phase I
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Bodilis, H., primary, Calin, R., additional, Ho Tsong Fang, R., additional, Launay, O., additional, Katlama, C., additional, Vieillard, V., additional, and Gharakhanian, S., additional
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- 2014
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7. Effects of zidovudine in 365 consecutive patients with AIDS or aids-related complex
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Dournon, E., Rozenbaum, W., Michon, C., Perronne, C., De Truchis, P., Bouvet, E., Levacher, M., Matheron, S., Gharakhanian, S., Girard, P.M., Salmon, D., Leport, C., Dazza, M.D., and Regnier, B.
- Subjects
AIDS (Disease) -- Drug therapy ,Pharmacology, Experimental -- Research ,Zidovudine -- Dosage and administration - Published
- 1988
8. 58 TREATMENT OF CHRONIC HEPATITIS C WITH TELAPREVIR (TVR) IN COMBINATION WITH PEGINTERFERON-ALFA-2A WITH OR WITHOUT RIBAVIRIN: FURTHER INTERIM ANALYSIS RESULTS OF THE PROVE2 STUDY
- Author
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Dusheiko, G.M., primary, Hezode, C., additional, Pol, S., additional, Goeser, T., additional, Bronowicki, J.-P., additional, Bourliere, M., additional, Buggisch, P., additional, Serfaty, L., additional, Berg, T., additional, Couzige, P., additional, Benhamou, Y., additional, Forestier, N., additional, Bengtsson, L., additional, Gharakhanian, S., additional, Kauffman, R., additional, Alam, J., additional, Ferenci, P., additional, Pawlotsky, J.-M., additional, and Zeuzem, S., additional
- Published
- 2008
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9. Effect of interferon alpha on high serum androgen concentrations in HIV positive men with Kaposi's sarcoma.
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Christeff, N, primary, Gharakhanian, S, additional, Thobie, N, additional, Wirbel, E, additional, Dalle, M T, additional, Costagliola, D, additional, Nunez, E A, additional, and Rozenbaum, W, additional
- Published
- 1997
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10. Cutaneous Local Necrosis Following Interferon Injections
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Cnudde, F., primary, Gharakhanian, S., additional, Luboinski, J., additional, Dry, J., additional, and Rozenbaum, W., additional
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- 1991
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11. Lenograstim for the treatment of neutropenia in patients receiving ganciclovir for cytomegalovirus infection: a randomised, placebo‐controlled trial in AIDS patients.
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Dubreuil‐Lemaire, M‐L., Gori, A., Vittecoq, D., Panelatti, G., Tharaux, F., Palisses, R., Gharakhanian, S., and Rozenbaum, W.
- Subjects
GRANULOCYTE-colony stimulating factor ,AIDS ,CYTOMEGALOVIRUS diseases ,NEUTROPHILS - Abstract
This phase IIa, randomised, single‐blind, placebo‐controlled study was conducted to determine the dose of recombinant human granulocyte colony‐stimulating factor (lenograstim) suitable for use in AIDS patients. The study was conducted at 27 European AIDS/HIV centres, and recruited 69 AIDS patients with an initial episode or relapse of cytomegalovirus infection (neurological site excluded) and an absolute neutrophil count (ANC) ≤1.0×10
9 /L upon diagnosis or between days 1 and 12 of ganciclovir (GCV) treatment. The patients were randomised to placebo (n=14) or one of four lenograstim arms: 150 µg/m2 /d (the standard onco‐haematology dose, n=13) or 100 (n=13), 50 (n=15), or 25 µg/m2 /d (n=14). In all groups, the planned dose of GCV was 10mg/kg/d for 21 d. Median ANC at weeks 2 and 3 was significantly higher in each lenograstim group than in the placebo group (p=0.05). At week 3, median ANC (×109 /L) was 0.7 in the placebo group, compared with 6.0, 7.4, 4.5, and 2.0 in the 150, 100, 50, and 25 µg2 /d lenograstim groups, respectively. Median ANC was not significantly different between the 150, 100, and 50 µg/m2 /d lenograstim groups at any time point, but significantly higher in the 50 than in the 25 µg/m2 /d group at weeks 2 (p=0.05) and 3 (p=0.02). Lenograstim was generally well tolerated, leading to no severe adverse events. In conclusion, lenograstim 50µg/m2 /d is suitable for the treatment of ganciclovir‐induced neutropenia and is safe. These results should help the physician choose an optimal and cost‐efficient regimen for patients with AIDS‐related neutropenia when rHuG‐CSF support is indicated. [ABSTRACT FROM AUTHOR]- Published
- 2000
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12. Activite et toxicite de la zidovudine (AZT). Etude prospective chez 365 malades atteints d'arc ou de SIDA
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DOURNON, E, primary, MATHERON, S, additional, ROZENBAUM, W, additional, GHARAKHANIAN, S, additional, MICHON, C, additional, GIRARD, P, additional, PERRONNE, C, additional, SALMON, D, additional, DETRUCHIS, P, additional, and LEPORT, C, additional
- Published
- 1988
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13. HIV AND OROGENITAL TRANSMISSION
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Dassey, DavidE, primary, Detels, R, additional, Visscher, B, additional, Rozenbaum, W, additional, Gharakhanian, S, additional, Gardon, B, additional, Duval, E, additional, and Coulaud, J.P, additional
- Published
- 1988
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14. Effect of interferon alpha on high serum androgen concentrations in HIV positive men with Kaposi's sarcoma
- Author
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Christeff, N., Gharakhanian, S., Thobie, N., Wirbel, E., Dalle, M.T., Costagliola, D., Nunez, E.A., and Rozenbaum, W.
- Subjects
Kaposi's sarcoma -- Physiological aspects -- Measurement ,Interferon alpha -- Physiological aspects -- Measurement ,Androgens -- Measurement -- Physiological aspects ,Health ,Physiological aspects ,Measurement - Abstract
Christeff, N.; Gharakhanian, S.; Thobie, N.; Wirbel, E.; Dalle, M.T.; Costagliola, D.; Nunez, E.A.; Rozenbaum, W. 'Effect of Interferon Alpha on High Serum Androgen Concentrations in HIV Positive Men with [...]
- Published
- 1997
15. Effect of interferon alpha on high serum concentrations in HIV positive men with Kaposi's sarcoma
- Author
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Christeff, N., Gharakhanian, S., Thobie, N., Wirbel, E., Dalle, M.T., Costagliola, D., Nunez, E.A., and Rozenbaum, W.
- Subjects
Kaposi's sarcoma -- Care and treatment ,Interferon alpha -- Physiological aspects - Abstract
Christeff, N.; Gharakhanian, S.; Thobie, N.; Wirbel, E.; Dalle, M.T.; Costagliola, D.; Nunez, E.A.; Rozenbaum, W. "Effect of Interferon Alpha on High Serum Androgen Concentrations in HIV Positive Men with [...]
- Published
- 1997
16. Serum cortisol/DHEA ratio during HIV infection
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Christeff, N., Gharakhanian, S., and Nunez, E.A.
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HIV infection -- Development and progression ,Hydrocortisone -- Physiological aspects ,Dehydroepiandrosterone -- Physiological aspects - Abstract
"Serum Cortisol/DHEA Ratio During HIV Infection." N. Christeff, S. Gharak- hanian, and E.A. Nunez. Laboratoire de Biochimie Endocrinienne et Biochimie B, Faculte de Medecine et Hopital X. Bichat, Paris; Service [...]
- Published
- 1997
17. Long-term efficacy of zidovudine (ZDV) in 169 patients with AIDS related complex
- Author
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Dournon, E., De Truchis, P., Leport, C., Gharakhanian, S., Gaudebout, C., and Matheron, S.
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AIDS-related complex -- Drug therapy ,Zidovudine -- Evaluation ,Business ,Health care industry - Abstract
AUTHORS: E. Dournon*, P. De Truchis, C. Leport, S. Gharakhanian, C. Gaudebout, S. Matheron, and ZDV Study Group. Bichat-Claude Bernard Hospital, Paris, France. According to the abstract of the authors' [...]
- Published
- 1990
18. Targeting GPVI with glenzocimab in COVID-19 patients: Results from a randomized clinical trial.
- Author
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Pottecher J, Raffi F, Jandrot-Perrus M, Binay S, Comenducci A, Desort-Henin V, François D, Gharakhanian S, Labart M, Meilhoc A, Toledano E, Pletan Y, Avenard G, and Sato VH
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Double-Blind Method, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized administration & dosage, Adult, Brazil, Treatment Outcome, COVID-19 Drug Treatment, COVID-19 complications, COVID-19 virology, SARS-CoV-2 drug effects, SARS-CoV-2 isolation & purification, Platelet Membrane Glycoproteins antagonists & inhibitors, Platelet Membrane Glycoproteins metabolism
- Abstract
Background: Glenzocimab is a novel antithrombotic agent which targets platelet glycoprotein VI (GPVI) and does not induce haemorrhage. SARS-CoV-2 triggers a prothrombotic state and lung injury whose mechanisms include coagulopathy, endothelial dysfunction, and inflammation with dysregulated platelets., Methods and Patients: GARDEN was a randomised double-blind, exploratory phase II study of glenzocimab in SARS-CoV-2 respiratory failure (NCT04659109). PCR+ adults in Brazil and France (7 centres) were randomized to standard-of-care (SOC) plus glenzocimab (1000 mg/dayx3 days) or placebo, followed for 40 days. Primary efficacy endpoint was clinical progression at Day 4. All analyses concerned the intention-to-treat population., Results: Between December 2020 and August 2021, 61 patients received at least one dose (30 glenzocimab vs 32 placebo) and 58 completed the study (29 vs 29). Clinical progression of COVID-19 ARDS was not statistically different between glenzocimab and placebo arms (43.3% and 29.0%, respectively; p = 0.245). Decrease in the NEWS-2 category at D4 was statistically significant (p = 0.0290) in the glenzocimab arm vs placebo. No Serious Adverse Event (SAE) was deemed related to study drug; bleeding related events were reported in 6 patients (7 events) and 4 patients (4 events) in glenzocimab and placebo arms, respectively., Conclusions: Therapeutic GPVI inhibition assessment during COVID-19 was conducted in response to a Public Health emergency. Glenzocimab in coagulopathic patients under therapeutic heparin was neither associated with increased bleeding, nor SAE. Clinical impact of glenzocimab on COVID-19 ARDS was not demonstrated. A potential role for GPVI inhibition in other types of ARDS deserves further experimentation. Glenzocimab is currently studied in stroke (ACTISAVE: NCT05070260) and cardiovascular indications., Competing Interests: The authors are declaring the following links of interest. JP was a part of GARDEN study scientific committee and worked as a consultant for Acticor Biotech, he also has link with AOP Orphan, Baxter, Edwards Lifseciences, Masimo, LFB, RDS and Takeda outside the scope of this work. FR has consultancy agreement with Astra Zeneca, Gilead, MSD, Roche and ViiV Healthcare. MJP is a scientific co-founder, consultant and shareholder of Acticor-Biotech. GA is a co-founder, CEO and shareholder of Acticor-Biotech. SB is the CSO and GM of Acticor Biotech. YP is the CMO and GM of Acticor Biotech as a consultant and has stock interest in Acticor Biotech. SB, AC, DF, ML, AM and ET are employees and have stock interest in Acticor Biotech. SG, VDH and GA are consultant for Acticor Biotech. Other authors have no links to disclose. Acticor Biotech is a commercial company currently developing GARDEN study drug, glenzocimab, and holds several related patents/rights. GARDEN study was an industry sponsored trial, and Acticor Biotech was involved, or provided support, for study design, data collection and analysis, decision to publish, and preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. , (Copyright: © 2024 Pottecher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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19. Evolution of weight and BMI during the course of HIV infection: historical perspective and challenges for clinical research.
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Gharakhanian S
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- Humans, Body Mass Index, HIV Infections complications, HIV-1
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- 2022
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20. Hypogonadism in HIV infection: time to fine-tune clinical monitoring of persons with HIV?
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Gharakhanian S and De Wit S
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- Humans, Testosterone, HIV Infections complications, Hypogonadism diagnosis
- Published
- 2022
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21. Potential use of serum-derived bovine immunoglobulin/protein isolate for the management of COVID-19.
- Author
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Utay NS, Asmuth DM, Gharakhanian S, Contreras M, Warner CD, and Detzel CJ
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- Angiotensin-Converting Enzyme 2 metabolism, Animals, COVID-19 complications, Cattle, Cytokine Release Syndrome etiology, Cytokine Release Syndrome prevention & control, Gastrointestinal Microbiome, Gastrointestinal Tract pathology, Humans, Permeability, Immunization, Passive methods, COVID-19 Drug Treatment
- Abstract
COVID-19 manifests as a mild disease in most people but can progress to severe disease in nearly 20% of individuals. Disease progression is likely driven by a cytokine storm, either directly stimulated by SARS-CoV-2 or by increased systemic inflammation in which the gut might play an integral role. SARS-CoV-2 replication in the gut may cause increased intestinal permeability, alterations to the fecal microbiome, and increased inflammatory cytokines. Each effect may lead to increased systemic inflammation and the transport of cytokines and inflammatory antigens from the gut to the lung. Few interventions are being studied to treat people with mild disease and prevent the cytokine storm. Serumderived bovine immunoglobulin/protein isolate (SBI) may prevent progression by (1) binding and neutralizing inflammatory antigens, (2) decreasing gut permeability, (3) interfering with ACE2 binding by viral proteins, and (4) improving the fecal microbiome. SBI is therefore a promising intervention to prevent disease progression in COVID-19 patients., (© 2021 The Authors. Drug Development Research published by Wiley Periodicals LLC.)
- Published
- 2021
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22. HIV therapeutic vaccine enhances non-exhausted CD4 + T cells in a randomised phase 2 trial.
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Vieillard V, Combadière B, Tubiana R, Launay O, Pialoux G, Cotte L, Girard PM, Simon A, Dudoit Y, Reynes J, Rockstroh J, Garcia F, Gatell J, Devidas A, Yazdanpanah Y, Weiss L, Fätkenheuer G, Autran B, Joyeux D, Gharakhanian S, Debré P, and Katlama C
- Abstract
VAC-3S is a therapeutic vaccine comprising a highly conserved HIV-gp41 motif coupled with the CRM197 carrier protein. High levels of anti-3S antibodies (Abs) have been associated with improved protection of CD4
+ T-cell survival. A previous phase 1 study demonstrated the safety of VAC-3S. This multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial enroled between January 2014 and March 2015 HIV-1-infected patients under ART with plasma HIV RNA levels below 50 copies/mL and CD4 counts between 200 and 500 cells/μL. Participants were immunised with 16, 32, or 64 μg of VAC-3S, and compared to placebo. The primary outcome was immunogenicity assessed by changes from baseline of anti-3S Abs levels at week 12. Secondary outcomes included adverse events and the course of plasma HIV RNA level, CD4 count, CD4/CD8 ratio, inflammation and immune checkpoints from week 0 to week 48. Vaccination was well tolerated with no serious adverse events and induced a significant increase in anti-3S Ab response in vaccinated patients ( p < 0.0001), compared to placebo. In high responders, the robust increased of CD4 count was associated with a significant and sustained reduction of PD-1 expression on CD4+ T cells through week 48 (variance p = 0.0017). PD-1 expression was correlated with level of anti-3S Abs ( p = 0.0092, r = -0.68) and expression of NKp44L ( p < 0.0001; r = 0.54) in CD4+ T cells. Our findings regarding the increase of non-exhausted CD4+ T cells have potentially important application in personalised HIV vaccination for HIV-infected patients with high level of PD-1 to improve their T-cell immune function., Competing Interests: Competing interestsV.V. and P.D. are founders of InnaVirVax and consultants for Minka Tx. B.C. is consultant for Minka Tx. S.G. has been consultant for InnaVirVax. D.J. is Chief Operative Officer of Minka Tx. The remaining authors declare no competing interests.- Published
- 2019
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23. Perspectives for immunotherapy: which applications might achieve an HIV functional cure?
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Vieillard V, Gharakhanian S, Lucar O, Katlama C, Launay O, Autran B, Ho Tsong Fang R, Crouzet J, Murphy RL, and Debré P
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- Animals, Anti-Retroviral Agents therapeutic use, Antibodies, Neutralizing immunology, CD4-Positive T-Lymphocytes immunology, HIV Envelope Protein gp120 immunology, HIV-1 immunology, Humans, Inflammation, Peptides immunology, Vaccination, Viral Load, HIV Infections immunology, HIV Infections therapy, Immunotherapy methods
- Abstract
The major advances achieved in devising successful combined antiretroviral therapy (cART) have enabled the sustained control of HIV replication. However, this is associated with costly lifelong treatment, partial immune restoration, chronic inflammation and persistent viral reservoirs. In this context, new therapeutic strategies deserve investigation as adjuncts to cART so as to potentiate immune responses that are capable of completely containing HIV pathogenicity, particularly if cART is discontinued. This may seem a dauntingly high hurdle given the results to date. This review outlines the key research efforts that have recently resurrected immunotherapeutic options, and some of the approaches tested to date. These areas include promising cytokines or vaccine strategies, using different viral or non-viral vectors based on polyvalent "mosaic" antigens and highly conserved HIV envelope peptides, broadly neutralizing antibodies or new properties of antibodies to improve the control of immune system homeostasis. These novel immunotherapeutic strategies appear promising per se, or in combination with TLR-agonists in order to bypass the complexity of the interplay between immune activation, massive CD4+ T-cell loss and viral persistence., Competing Interests: CONFLICTS OF INTERESTS SG has been consultant for InnaVirVax. RHTF is employee of InnaVirVax. JC is founder, Chief Executive Officer and shareholder of InnaVirVax. PD and VV are founders and shareholders of InnaVirVax. All other authors declare no conflict of interests.
- Published
- 2016
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24. Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial.
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Sulkowski MS, Sherman KE, Dieterich DT, Bsharat M, Mahnke L, Rockstroh JK, Gharakhanian S, McCallister S, Henshaw J, Girard PM, Adiwijaya B, Garg V, Rubin RA, Adda N, and Soriano V
- Subjects
- Adult, Anti-HIV Agents therapeutic use, Antiviral Agents adverse effects, Antiviral Agents pharmacokinetics, Double-Blind Method, Drug Therapy, Combination, Female, Genotype, HIV-1, Hepacivirus genetics, Hepatitis C, Chronic virology, Humans, Interferon-alpha adverse effects, Interferon-alpha pharmacokinetics, Interferon-alpha therapeutic use, Male, Middle Aged, Oligopeptides adverse effects, Oligopeptides pharmacokinetics, Polyethylene Glycols adverse effects, Polyethylene Glycols pharmacokinetics, Polyethylene Glycols therapeutic use, Recombinant Proteins adverse effects, Recombinant Proteins pharmacokinetics, Recombinant Proteins therapeutic use, Ribavirin adverse effects, Ribavirin pharmacokinetics, Ribavirin therapeutic use, Treatment Outcome, Antiviral Agents therapeutic use, HIV Infections complications, Hepatitis C, Chronic drug therapy, Oligopeptides therapeutic use
- Abstract
Background: Telaprevir (TVR) plus peginterferon-α2a (PEG-IFN-α2a) and ribavirin substantially increases treatment efficacy for genotype 1 chronic hepatitis C virus (HCV) infection versus PEG-IFN-α2a-ribavirin alone. Its safety and efficacy in patients with HCV and HIV-1 are unknown., Objective: To assess the safety and efficacy of TVR plus PEG-IFN-α2a-ribavirin in patients with genotype 1 HCV and HIV-1 and to evaluate pharmacokinetics of TVR and antiretrovirals during coadministration., Design: Phase 2a, randomized, double-blind, placebo-controlled study. (ClinicalTrials.gov: NCT00983853)., Setting: 16 international multicenter sites., Patients: 62 patients with HCV genotype 1 and HIV-1 who were HCV treatment-naive and receiving 0 or 1 of 2 antiretroviral regimens were randomly assigned to TVR plus PEG-IFN-α2a-ribavirin or placebo plus PEG-IFN-α2a-ribavirin for 12 weeks, plus 36 weeks of PEG-IFN-α2a-ribavirin., Measurements: HCV RNA concentrations., Results: Pruritus, headache, nausea, rash, and dizziness were higher with TVR plus PEG-IFN-α2a-ribavirin during the first 12 weeks. During this period, serious adverse events occurred in 5% (2 in 38) of those receiving TVR plus PEG-IFN-α2a-ribavirin and 0% (0 in 22) of those receiving placebo plus PEG-IFN-α2a-ribavirin; the same number in both groups discontinued treatment due to adverse events. Sustained virologic response occurred in 74% (28 in 38) of patients receiving TVR plus PEG-IFN-α2a-ribavirin and 45% (10 in 22) of patients receiving placebo plus PEG-IFN-α2a-ribavirin. Rapid HCV suppression was seen with TVR plus PEG-IFN-α2a-ribavirin (68% [26 in 38 patients] vs. 0% [0 in 22 patients] undetectable HCV RNA levels by week 4). Two patients had on-treatment HCV breakthrough with TVR-resistant variants. Patients treated with antiretroviral drugs had no HIV breakthroughs; antiretroviral exposure was not substantially modified by TVR., Limitation: Small sample size and appreciable dropout rate., Conclusion: In patients with HCV and HIV-1, more adverse events occurred with TVR versus placebo plus PEG-IFN-α2a-ribavirin; these were similar in nature and severity to those in patients with HCV treated with TVR. With or without concomitant antiretrovirals, sustained virologic response rates were higher in patients treated with TVR versus placebo plus PEG-IFN-α2a-ribavirin.
- Published
- 2013
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25. Diabetes mellitus, HIV infection, and vitamin D: time to act or time to think?
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Gharakhanian S and Kotler DP
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- Diabetes Mellitus, Type 2 drug therapy, HIV Infections complications, Humans, Vitamin D administration & dosage, Vitamin D Deficiency complications, HIV Infections drug therapy, Vitamin D analogs & derivatives, Vitamin D Deficiency drug therapy
- Published
- 2011
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26. Merimepodib, pegylated interferon, and ribavirin in genotype 1 chronic hepatitis C pegylated interferon and ribavirin nonresponders.
- Author
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Rustgi VK, Lee WM, Lawitz E, Gordon SC, Afdhal N, Poordad F, Bonkovsky HL, Bengtsson L, Chandorkar G, Harding M, McNair L, Aalyson M, Alam J, Kauffman R, Gharakhanian S, and McHutchison JG
- Subjects
- Adolescent, Adult, Aged, Carbamates adverse effects, Carbamates pharmacokinetics, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Interferon alpha-2, Male, Middle Aged, Phenylurea Compounds adverse effects, Phenylurea Compounds pharmacokinetics, Recombinant Proteins, Antiviral Agents administration & dosage, Carbamates administration & dosage, Hepatitis C, Chronic drug therapy, Interferon-alpha administration & dosage, Phenylurea Compounds administration & dosage, Polyethylene Glycols administration & dosage, Ribavirin administration & dosage
- Abstract
Unlabelled: Merimepodib (MMPD) is an orally administered, inosine monophosphate dehydrogenase inhibitor that has shown antiviral activity in nonresponders with chronic hepatitis C (CHC) when combined with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) and ribavirin (RBV). We conducted a randomized, double-blind, multicenter, phase 2b study to evaluate the antiviral activity, safety, and tolerability of MMPD in combination with Peg-IFN-alfa-2a and RBV in patients with genotype 1 CHC who were nonresponders to prior therapy with Peg-IFN and RBV. Patients received 50 mg MMPD, 100 mg MMPD, or placebo every 12 hours, in addition to Peg-IFN-alfa-2a and RBV, for 24 weeks. Patients with a 2-log or more decrease from baseline or undetectable hepatitis C virus (HCV) RNA levels at week 24 were then eligible to continue Peg-IFN-alfa-2a and RBV for a further 24 weeks, followed by 24 weeks of follow-up. The primary efficacy endpoint was sustained virological response (SVR) rate at week 72 in all randomized patients who received at least one dose of study drug and had a history of nonresponse to standard therapy. A total of 354 patients were randomized to treatment (117 to placebo; 119 to 50 mg MMPD; 118 to 100 mg MMPD), and 286 completed the core study. The proportion of patients who achieved SVR was similar among the treatment groups: 6% (6/107) for 50 mg MMPD, 4% (5/112) for 100 mg MMPD, and 5% (5/104) for placebo (P = 0.8431). Adverse-event profiles for the MMPD combination groups were similar to that for Peg-IFN-alfa and RBV alone. Nausea, arthralgia, cough, dyspnea, neutropenia, and anemia were more common in patients taking MMPD., Conclusion: The addition of MMPD to Peg-IFN-alfa-2a and RBV combination therapy did not increase the proportion of nonresponder patients with genotype 1 CHC achieving an SVR.
- Published
- 2009
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27. Telaprevir and peginterferon with or without ribavirin for chronic HCV infection.
- Author
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Hézode C, Forestier N, Dusheiko G, Ferenci P, Pol S, Goeser T, Bronowicki JP, Bourlière M, Gharakhanian S, Bengtsson L, McNair L, George S, Kieffer T, Kwong A, Kauffman RS, Alam J, Pawlotsky JM, and Zeuzem S
- Subjects
- Adult, Aged, Antiviral Agents adverse effects, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Genotype, Hepacivirus isolation & purification, Hepatitis C, Chronic virology, Humans, Interferon alpha-2, Interferon-alpha adverse effects, Male, Middle Aged, Oligopeptides adverse effects, Polyethylene Glycols adverse effects, RNA, Viral blood, Recombinant Proteins, Recurrence, Ribavirin adverse effects, Viral Load, Young Adult, Antiviral Agents therapeutic use, Hepacivirus genetics, Hepatitis C, Chronic drug therapy, Interferon-alpha therapeutic use, Oligopeptides therapeutic use, Polyethylene Glycols therapeutic use, Ribavirin therapeutic use
- Abstract
Background: In patients with chronic infection with hepatitis C virus (HCV) genotype 1, treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50%. Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment., Methods: A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were randomly assigned to receive one of four treatments involving various combinations of telaprevir (1250 mg on day 1, then 750 mg every 8 hours), peginterferon alfa-2a (180 microg weekly), and ribavirin (dose according to body weight). The T12PR24 group (81 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks, followed by peginterferon alfa-2a and ribavirin for 12 more weeks. The T12PR12 group (82 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks. The T12P12 group (78 patients) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks. The PR48 (control) group (82 patients) received peginterferon alfa-2a and ribavirin for 48 weeks. The primary end point, a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy), was compared between the control group and the combined T12P12 and T12PR12 groups., Results: The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48% (77 of 160 patients), as compared with 46% (38 of 82) in the PR48 (control) group (P=0.89). The rate was 60% (49 of 82 patients) in the T12PR12 group (P=0.12 for the comparison with the PR48 group), as compared with 36% (28 of 78 patients) in the T12P12 group (P=0.003; P=0.20 for the comparison with the PR48 group). The rate was significantly higher in the T12PR24 group (69% [56 of 81 patients]) than in the PR48 group (P=0.004). The adverse events with increased frequency in the telaprevir-based groups were pruritus, rash, and anemia., Conclusions: In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy. Response rates were lowest with the regimen that did not include ribavirin. (ClinicalTrials.gov number, NCT00372385.), (2009 Massachusetts Medical Society)
- Published
- 2009
- Full Text
- View/download PDF
28. Statins in HIV-associated lipodystrophy and metabolic syndrome: is there a missing link?
- Author
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Gharakhanian S, Boccara F, and Capeau J
- Subjects
- Cardiovascular Diseases complications, Cardiovascular Diseases prevention & control, Cholesterol blood, HIV Infections complications, HIV Protease Inhibitors therapeutic use, HIV-Associated Lipodystrophy Syndrome drug therapy, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Male, Treatment Outcome, Anticholesteremic Agents therapeutic use, HIV Infections drug therapy, Metabolic Syndrome drug therapy, Pravastatin therapeutic use
- Published
- 2006
- Full Text
- View/download PDF
29. [Adherence to antiretroviral therapy during HIV infection, a multidisciplinary approach].
- Author
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Slama L, Le Camus C, Amiel C, Pialoux G, and Gharakhanian S
- Subjects
- Anti-HIV Agents administration & dosage, Anti-HIV Agents adverse effects, Anti-HIV Agents pharmacokinetics, Antiretroviral Therapy, Highly Active, Clinical Trials as Topic methods, Clinical Trials as Topic statistics & numerical data, Cohort Studies, Drug Therapy, Combination, Food-Drug Interactions, HIV Infections epidemiology, HIV Infections psychology, Humans, Interdisciplinary Communication, Outcome Assessment, Health Care, Patient Care Team, Physician-Patient Relations, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Treatment Refusal statistics & numerical data
- Abstract
Since HIV infection has become a chronic disease, antiretroviral therapy is now used on a long-term basis. Response to treatment is conditioned by numerous inter-dependent factors, including non-compliance, which can result in failure of the therapeutic regimen. Although compliance is crucial for long-term efficacy of the treatment, it is a dynamic factor, and therefore difficult to evaluate. This literature review proposes a multidisciplinary approach to treatment adherence during HIV infection, and deals with the following questions: how should adherence and non-adherence be defined? How are they correlated to the treatment response? How is adherence measured in trials and cohorts, as well as in clinical practice? By what factors is it influenced? What tools can be implemented to improve adherence? The interaction between adherence and response to antiretroviral therapy requires communication between clinicians, healthcare providers, patients, virologists, pharmacologists, and the companies responsible for developing drugs. The pharmaceutical industry must sustain its efforts to ensure a balance between demands for efficacy and adherence when developing new drugs. And the methods implemented by numerous healthcare teams plead in favour of a dynamic approach to adherence, with the active participation of all.
- Published
- 2006
- Full Text
- View/download PDF
30. Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy.
- Author
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Vigouroux C, Maachi M, Nguyên TH, Coussieu C, Gharakhanian S, Funahashi T, Matsuzawa Y, Shimomura I, Rozenbaum W, Capeau J, and Bastard JP
- Subjects
- Adiponectin, Adult, Aged, Antigens, CD blood, Antiretroviral Therapy, Highly Active, Apolipoproteins A analysis, Apolipoproteins B analysis, C-Reactive Protein analysis, Cholesterol blood, HIV Infections drug therapy, HIV-Associated Lipodystrophy Syndrome blood, HIV-Associated Lipodystrophy Syndrome drug therapy, Humans, Interleukin-6 blood, Leptin blood, Male, Middle Aged, Proteins analysis, Receptors, Tumor Necrosis Factor blood, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Regression Analysis, Triglycerides blood, Tumor Necrosis Factor-alpha analysis, Adipose Tissue immunology, Anti-HIV Agents therapeutic use, Cytokines blood, HIV-1, HIV-Associated Lipodystrophy Syndrome immunology, Intercellular Signaling Peptides and Proteins
- Abstract
Objectives: Adipocytokines, secreted by adipose tissue, may regulate fat metabolism, lipid and glucose homeostasis and insulin sensitivity. We analysed the relations between circulating concentrations of adiponectin, leptin, interleukin-6, tumor necrosis factor alpha and its soluble receptors sTNFR1 and R2, lipodystrophic phenotypes and metabolic alterations in patients under highly active antiretroviral therapy (HAART)., Methods: We studied 131 consecutive HIV-infected males under protease inhibitor (PI)-based HAART, with body mass index < 27 kg/m2 and C-reactive protein (CRP) < 10 mg/l. Patients were classified in four groups according to clinical examination: no lipodystrophy (NL), lipohypertrophy (LH), lipoatrophy (LA) and mixed lipodystrophy (ML). In addition to adipocytokines, we measured plasma fasting levels of triglycerides, cholesterol, cardiovascular risk markers (high-sensitivity CRP and apolipoproteins B/A1 ratio), fasted and 2 h post-glucose loading glycemia and insulinemia and calculated the quantitative insulin sensitivity check index., Results: The patients were HIV-infected and PI-treated for a mean of 8.2 and 1.6 years respectively; 74% presented lipodystrophy, 38% altered glucose tolerance and 42% hypertriglyceridemia. Insulin sensitivity correlated positively with adiponectin and negatively with leptin and interleukin-6. Adiponectin, but not leptin, negatively correlated with all metabolic parameters. Insulin resistance, metabolic defects and cardiovascular risk markers were strongly negatively correlated with the adiponectin/leptin ratio (A/L), and positively with sTNFR1. LA patients had a longer duration of infection but ML patients presented the most severe metabolic alterations, insulin resistance and A/L decrease., Conclusions: These results suggest that adiponectin and the TNFalpha system are related to lipodystrophy, insulin resistance and metabolic alterations in patients under PI-based HAART. A/L and sTNFR1 could predict insulin sensitivity and potential cardiovascular risk in these patients.
- Published
- 2003
- Full Text
- View/download PDF
31. The HIV-associated lipodystrophy syndrome: research, results, yet more questions.
- Author
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Gharakhanian S
- Subjects
- Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy, HIV Infections metabolism, HIV Protease Inhibitors adverse effects, HIV Protease Inhibitors therapeutic use, Humans, Lipodystrophy metabolism, Research, Syndrome, HIV Infections complications, Lipodystrophy etiology
- Published
- 2001
- Full Text
- View/download PDF
32. Treatment of severe seasonal rhinoconjunctivitis by a combination of azelastine nasal spray and eye drops: a double-blind, double-placebo study.
- Author
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Duarte C, Baëhre M, Gharakhanian S, and Leynadier F
- Subjects
- Adult, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Severity of Illness Index, Treatment Outcome, Administration, Intranasal, Anti-Allergic Agents administration & dosage, Anti-Allergic Agents therapeutic use, Conjunctivitis, Allergic therapy, Ophthalmic Solutions therapeutic use, Phthalazines administration & dosage, Phthalazines therapeutic use, Rhinitis, Allergic, Seasonal therapy
- Abstract
Background: Evaluation of combined azelastine nasal spray and eye drops treatment in patients with severe rhinoconjunctivitis., Methods: Phase III, multicenter, randomized, double-blind study of patients with a history of grass pollen allergy, confirmed by skin testing/specific IgE, total symptom scores > or =6 (ocular) or > or =8 (nasal). Intent-to-treat analysis., Results: 99 patients (azelastine = 53, placebo = 46) enrolled homogeneously from May to September 1997 in 7 venues in France. The efficacy of azelastine was significantly higher compared to placebo (49% vs. 28%, p = 0.04), considering response as a decrease of the total sum of ocular and nasal scores by at least 50% and no use of cetirizine by day 7. The decrease of total ocular and nasal scores by at least 50% at day 7, with cetirizine rescue <3 tablets was higher, but not significantly, in azelastine patients (43% vs. 30%). Cetirizine rescue was more frequent, from day 0 to 7, in the placebo patients (4.9 +/- 5.0 vs. 2.7 +/- 4.1, p = 0.02). Global efficacy was rated higher for azelastine by investigators (26% vs. 10%, p = 0.05) and patients (28% vs. 7%, p = 0.01). Adverse events were burning sensation, "red eyes," nasal irritation, bitter taste. No serious adverse events were reported. Tolerance of azelastine was "very good/good"/"satisfactory" in the majority (62%/82% assessed by investigators, or 55%/79% by patients, respectively)., Conclusions: Combining azelastine eye drops and nasal spray is a safe and effective treatment of severe seasonal rhinoconjunctivitis.
- Published
- 2001
33. Adverse metabolic disorders during highly active antiretroviral treatments (HAART) of HIV disease.
- Author
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Vigouroux C, Gharakhanian S, Salhi Y, Nguyên TH, Adda N, Rozenbaum W, and Capeau J
- Subjects
- HIV Protease Inhibitors adverse effects, Humans, Hyperglycemia chemically induced, Hyperlipidemias chemically induced, Insulin Resistance, Metabolic Diseases physiopathology, Metabolic Diseases therapy, Reverse Transcriptase Inhibitors adverse effects, Anti-HIV Agents adverse effects, HIV Infections drug therapy, Metabolic Diseases chemically induced
- Abstract
Protease inhibitor treatment has dramatically improved rates of morbidity and mortality in HIV-infected patients. However, it has recently been shown that this medication is associated with long-term side effects characterized by metabolic, clinical and biological alterations. These modifications have been described in patients treated with highly active antiretroviral therapy (HAART), including nucleoside analogue reverse transcriptase inhibitors (NRTI) and generally (but not always) protease inhibitors (PI). Clinical alterations are characterised by a body fat redistribution syndrome or lipodystrophy, with peripheral lipoatrophy and/or central fat accumulation. They are often associated with biological alterations, i.e. insulin resistance, hyperglycaemia and dyslipidaemia, which can also be observed alone. The pathophysiology of these alterations is presently unknown. The deleterious effect of PI on adipose tissue could be direct or indirect, and is probably modulated by genetic or environmental factors. NRTI could also be involved because of their mitochondrial toxicity. The purpose of the treatment is to control metabolic disturbances in order to prevent immediate complications such as acute pancreatitis and limit possible cardiovascular and diabetic complications at longer term. Studies are in progress to evaluate the possibility of therapeutic alternatives to PI when major metabolic disturbances are present.
- Published
- 1999
34. Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART).
- Author
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Vigouroux C, Gharakhanian S, Salhi Y, Nguyen TH, Chevenne D, Capeau J, and Rozenbaum W
- Subjects
- Adult, Aged, Apolipoproteins blood, Blood Glucose metabolism, Cholesterol blood, Drug Therapy, Combination, Fatty Acids, Nonesterified blood, Female, Glucose Tolerance Test, Humans, Insulin blood, Lipodystrophy physiopathology, Male, Middle Aged, Proinsulin blood, Retrospective Studies, Triglycerides blood, Anti-HIV Agents adverse effects, Diabetes Mellitus etiology, HIV Infections drug therapy, HIV Protease Inhibitors adverse effects, Hyperlipidemias etiology, Insulin Resistance, Lipodystrophy chemically induced
- Abstract
This study assessed glucose tolerance, insulin sensitivity and lipid parameters in HIV-infected patients presenting with lipodystrophy during HAART including protease inhibitors. Fourteen consecutive patients from Rothschild Hospital treated with HAART and presenting with marked facial lipoatrophy were evaluated. A 75 g oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, proinsulin and free fatty acids at T0, 30, 60, 90 and 120 min was performed. Lipid parameters (triglycerides, cholesterol, apolipoproteins A1 and B) were studied as well as nutritional and inflammatory markers (albumin, prealbumin, transferrin, haptoglobin, orosomucoid, C-reactive protein), endocrine and cytokine parameters (thyrotropin, cortisol, leptin, interleukin-6), HIV viral load and CD4-lymphocyte count. These patients were compared with 20 non-lipodystrophic protease inhibitor-treated patients. The measurements performed during OGTT showed that among the 14 lipodystrophic patients, 11 (79%) presented with diabetes (5 patients) or normal glucose tolerance but with insulin resistance (6 patients). This frequency was strikingly different in the group of nonlipodystrophic patients, which included only 4 (20%) presenting with diabetes (1 patient), or impaired glucose tolerance (2 patients), or normal glucose tolerance but with insulin resistance (1 patient). Hypertriglyceridaemia was present in 11 lipodystrophic (79%) versus 7 nonlipodystrophic patients (35%). Nutritional and endocrine measurements were normal. An abnormal processing of proinsulin to insulin was excluded. Thus, lipodystrophy during HAART was associated with diabetes, insulin resistance and hypertriglyceridaemia. Diabetes, diagnosed by basal and/or 120 min-OGTT glycaemia, seems more frequent than previously described. The therapeutic consequences of these results deserve evaluation in clinical trials.
- Published
- 1999
35. Serum cortisol and DHEA concentrations during HIV infection.
- Author
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Christeff N, Gherbi N, Mammes O, Dalle MT, Gharakhanian S, Lortholary O, Melchior JC, and Nunez EA
- Subjects
- Adult, Blotting, Western, CD4-CD8 Ratio, Cachexia pathology, HIV Infections physiopathology, HIV Seropositivity, Humans, Male, Prospective Studies, Retrospective Studies, Weight Loss physiology, Dehydroepiandrosterone blood, HIV Infections blood, Hydrocortisone blood
- Abstract
The progression of HIV infection is accompanied by severe immunodepression and cachexia, particularly during advanced stages. The immune depression is due largely to a dramatic drop in the number of CD4 cells. The loss of body weight is mainly due to a reduced fat-free mass with no change in adipose tissue. We determined the serum concentrations of cortisol and DHEA and their correlations with absolute CD4 cell counts and changes in body weight of HIV-positive men. The results of five retrospective and prospective studies indicate that the serum concentrations of cortisol and DHEA in HIV-infected patients were different from those of HIV-negative controls. Serum cortisol was elevated at all stages of infection (+20 to +50%, p < .05 to p < .001) particularly in AIDS patients (stage IV C). In contrast, the serum DHEA concentrations were closely correlated with the stage of HIV-infection, being higher in the early stages (stages II and III or > 500 CD4) than in advanced stages (IV C or < 500 CD4)-in the latter being below those of HIV-negative men-or in controls (+40 to 100%, p < .01 to p < .001). There was a negative linear correlation between the CD4 cell counts and cortisol (r = -0.4, p < .02) and a positive linear correlation with DHEA (r = +0.36, p < .01). There was no significant correlation between delta body weight and serum cortisol. In contrast, there was a negative correlation between serum DHEA and delta body weight (%) (r = -0.69, p < .0001) and a positive correlation with the cortisol/DHEA ratio (r = +0.61, p < .0001). There is thus a link between the circulating concentrations of adrenal steroids and the progression of immunosuppression and cachexia during HIV-infection. This raises the question of whether there is a cause-and-effect relationship between clinical progression and circulating steroid concentrations. Further investigations into the relationship between the ratio cortisol/DHEA and the immune response and cachexia should indicate the contributions of these steroids to the etiology of HIV infection and lead to the development of new therapeutic strategies.
- Published
- 1997
- Full Text
- View/download PDF
36. Etiology and management of toxic megacolon in patients with human immunodeficiency virus infection.
- Author
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Beaugerie L, Ngô Y, Goujard F, Gharakhanian S, Carbonnel F, Luboinski J, Malafosse M, Rozenbaum W, and Le Quintrec Y
- Subjects
- Adult, Anti-Bacterial Agents therapeutic use, Clostridioides difficile, Colectomy, Colonoscopy, Cytomegalovirus Infections complications, Cytomegalovirus Infections drug therapy, Enterocolitis, Pseudomembranous complications, Enterocolitis, Pseudomembranous drug therapy, Humans, Male, Megacolon, Toxic diagnostic imaging, Radiography, Survival Analysis, HIV Infections complications, Megacolon, Toxic microbiology, Megacolon, Toxic therapy
- Abstract
We report six cases of toxic megacolon in patients with human immunodeficiency virus (HIV). One case, at an early stage of HIV infection, mimicked a severe attack of Crohn's disease, with a negative search for infectious agents. Subtotal colectomy was successfully performed with an uneventful postoperative course. The five other cases concerned patients with acquired immunodeficiency syndrome at a late stage of immunodeficiency. They were related to Clostridium difficile or cytomegalovirus (CMV) intestinal infection in two and three patients, respectively. One case of CMV colitis presented macroscopically and histologically as pseudomembranous colitis. Emergency subtotal colectomy, performed in the first four patients with acquired immunodeficiency syndrome was followed by a fatal postoperative outcome. The last patient treated conservatively by colonoscopic decompression, in association with anti-CMV therapy, had a favorable short-term outcome. From the experience of our series and data from the literature, we discuss the best diagnostic and therapeutic approach to toxic megacolon in patients with HIV.
- Published
- 1994
- Full Text
- View/download PDF
37. Evidence for changes in adrenal and testicular steroids during HIV infection.
- Author
-
Christeff N, Gharakhanian S, Thobie N, Rozenbaum W, and Nunez EA
- Subjects
- 17-alpha-Hydroxyprogesterone, Adolescent, Adult, Androstenedione blood, Dehydroepiandrosterone analogs & derivatives, Dehydroepiandrosterone blood, Dehydroepiandrosterone Sulfate, Estradiol blood, Estrone blood, Humans, Hydrocortisone blood, Hydroxyprogesterones blood, Male, Middle Aged, Progesterone blood, Radioimmunoassay, Testosterone blood, Adrenal Cortex Hormones blood, HIV Infections blood, Testicular Hormones blood
- Abstract
The serum levels of cortisol, progesterone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione (delta 4), testosterone (T), estrone, and estradiol of HIV+ men and HIV- men were determined by radioimmunoassay. The cortisol, 17 alpha-hydroxyprogesterone, and estrone levels of all HIV+ subjects were 35-55% (p less than 0.01), 25-90% (p less than 0.01), and 30-50% (p less than 0.01) higher, respectively, than those of controls. Androgen levels were very high in Centers for Disease Control (CDC) groups II and III of HIV infection (DHEA, 85%, p less than 0.01; delta 4, 60%, p less than 0.01; T, 30%, p less than 0.05), but much lower in group IVC1 and IVC2. The estradiol levels were significantly elevated only in group IVD (50%, p less than 0.01) and group IVC2 (25%, NS). These results indicate that serum hormone levels are correlated with HIV infection group. The changes in steroid hormone concentrations during the development of HIV infection may have important implications for the immune response of patients. The high cortisol and estrone levels of all groups, the elevated androgen levels in asymptomatic groups, and the low androgens in AIDS patients may form part of the complex network of immunomodulatory factors.
- Published
- 1992
38. [Long-term effects of splenectomy for immune thrombopenic purpura related to human immunodeficiency virus. A retrospective study from 2 groups, with and without splenectomy].
- Author
-
Gabarre J, Azar N, Ben Othman T, Gharakhanian S, De Sahb R, Dohin E, Sansonetti P, Langlois P, Chigot JP, and Echard M
- Subjects
- Adult, Evaluation Studies as Topic, Female, Follow-Up Studies, HIV Seropositivity complications, Humans, Leukocyte Count, Lymphocyte Subsets, Lymphocytes, Male, Purpura, Thrombocytopenic, Idiopathic blood, Purpura, Thrombocytopenic, Idiopathic etiology, Retrospective Studies, Time Factors, Acquired Immunodeficiency Syndrome complications, Purpura, Thrombocytopenic, Idiopathic surgery, Splenectomy
- Abstract
In order to evaluate the long-term effects of splenectomy in patients with human immunodeficiency virus-related immune thrombocytopenic purpura (ITP), we studied retrospectively two populations of patients: 21 had undergone splenectomy and 18 had not. At the time of diagnosis the first population had on average lower platelet counts than the second one. After a mean follow-up of 47 +/- 9 months the situation has been reversed: the population that underwent splenectomy had significantly higher platelet counts than that without splenectomy (190.600 +/- 55.300/mm3 versus 91.500 +/- 55.300/mm3, P less than 0.001). Moreover 76 percent of the patients with splenectomy versus 50 percent in the population without splenectomy were in complete remission of ITP at the last follow-up. It therefore seems that splenectomy had a statistically positive effect on platelet counts without worsening the immune status. Indeed, the clinical course towards AIDS was the same in both populations (35 percent in patients with splenectomy and 22 percent without, P = NS). Following splenectomy, the total blood lymphocytes count was increased, especially the CD8 population, while the CD4 count remains unchanged; these findings seem to be a common feature after splenectomy.
- Published
- 1991
39. Efficacy and tolerance of intravitreal ganciclovir in cytomegalovirus retinitis in acquired immune deficiency syndrome.
- Author
-
Cochereau-Massin I, Lehoang P, Lautier-Frau M, Zazoun L, Marcel P, Robinet M, Matheron S, Katlama C, Gharakhanian S, and Rozenbaum W
- Subjects
- Adult, Drug Tolerance, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prospective Studies, Retinal Detachment etiology, Retinitis microbiology, Vitreous Body, Vitreous Hemorrhage etiology, Acquired Immunodeficiency Syndrome complications, Cytomegalovirus Infections drug therapy, Eye Infections, Viral drug therapy, Ganciclovir therapeutic use, Retinitis drug therapy
- Abstract
Forty-four patients with acquired immune deficiency syndrome with cytomegalovirus (CMV) retinitis (64 eyes) intolerant of or refusing systemic antiviral therapy received 710 intravitreal injections of ganciclovir at the dosage of 400 micrograms per injection. The patients were followed for a mean period of 9 weeks. Induction therapy consisted of two injections a week until healing. Maintenance therapy consisted of one injection a week until relapse. All but 1 of 53 induction courses led to cicatrization, after a mean of 6.6 injections. In 54 maintenance courses, the 8-week relapse rate was 53%. During intravitreal therapy, involvement of the fellow eye occurred in 11% of the patients and CMV infection developed in a nonocular site in 16% of the patients. Five retinal detachments and two intravitreal hemorrhages occurred. No endophthalmitis or cataract was noted. Intravitreal ganciclovir appears to be a safe and effective alternative in patients intolerant of intravenous anti-CMV drugs.
- Published
- 1991
- Full Text
- View/download PDF
40. Long-term follow-up of 120 patients with AIDS-related Kaposi's sarcoma treated with interferon alpha-2a.
- Author
-
Rozenbaum W, Gharakhanian S, Navarette MS, De Sahb R, Cardon B, and Rouzioux C
- Subjects
- Adult, Antigens, CD analysis, Antigens, Differentiation, T-Lymphocyte analysis, CD4 Antigens analysis, CD8 Antigens, Humans, Interferon alpha-2, Interferon-alpha adverse effects, Male, Middle Aged, Opportunistic Infections complications, Recombinant Proteins, Sarcoma, Kaposi etiology, Sarcoma, Kaposi immunology, Survival Analysis, Acquired Immunodeficiency Syndrome complications, Interferon-alpha therapeutic use, Sarcoma, Kaposi drug therapy
- Abstract
One hundred and twenty patients suffering from an AIDS-related Kaposi's sarcoma treated by 18 million units of recombinant alpha-2A-interferon daily were followed prospectively for a period of between one and six years. An overall complete response was observed in 35% of these patients; the figure was significantly higher in those who did not have a visceral localization or opportunistic infections. Total lymphocyte count, CD4 lymphocyte count, and CD4/CD8 ratio were significantly higher, and beta-2-microglobuline significantly lower, in the responders than in the non-responders. A multivariate analysis showed that localization of KS and CD4 count had independent predictive value, with an odds ratio of 35 for patients who had more than 300 CD4 cells at the onset of treatment versus those with less than 150. Patients whose initially negative p24 antigenemia remained negative during treatment had the highest frequency of complete response. Among patients with initially positive p24 antigenemia, those whose percentage decrease in antigenemia levels was greatest had a higher frequency of complete response. The cumulative probability of survival in responders was 62% at four years. These results demonstrate an anti-tumoral and anti-viral effect and prolonged survival in a group of patients whose initial immune parameters were relatively well preserved. However, these results do not permit us to conclude whether these well-responding patients were treated at the onset of illness, or whether their illness was naturally less evolutive.
- Published
- 1990
- Full Text
- View/download PDF
41. Vitamin B12 injections in patients treated with zidovudine.
- Author
-
Gharakhanian S, Navarette MS, Cardon B, and Rozenbaum W
- Subjects
- Anemia blood, Anemia chemically induced, Anemia prevention & control, Clinical Trials as Topic, Drug Therapy, Combination, HIV Infections blood, Humans, Zidovudine adverse effects, HIV Infections drug therapy, Vitamin B 12 administration & dosage, Zidovudine administration & dosage
- Published
- 1990
- Full Text
- View/download PDF
42. Unusual cutaneous cytomegalovirus involvement in patients with acquired immunodeficiency syndrome.
- Author
-
Bournérias I, Boisnic S, Patey O, Deny P, Gharakhanian S, Duflo B, and Gentilini M
- Subjects
- Adult, Biopsy, Blotting, Southern, Cytomegalovirus genetics, DNA, Viral analysis, Humans, Male, Middle Aged, Skin pathology, Acquired Immunodeficiency Syndrome complications, Cytomegalovirus Infections pathology, Skin Diseases, Infectious pathology
- Abstract
Two patients with acquired immunodeficiency syndrome presented unusual keratotic cutaneous lesions with a protracted course. Pathologic examination in both patients, cultures, and DNA hybridization techniques of skin biopsy specimens in the second patient were characteristic of cytomegalovirus cutaneous infection. Cytomegalovirus skin lesions are rarely described in acquired immunodeficiency syndrome in contrast with the high frequency of ocular and visceral involvement. Skin biopsy specimens may lead to early diagnosis of cytomegalovirus disseminated disease and to specific treatment.
- Published
- 1989
- Full Text
- View/download PDF
43. [Psychosocial consequences of HIV infection].
- Author
-
Pollak M, Rozenbaum W, Viallefont A, Gharakhanian S, and Aime F
- Subjects
- Acquired Immunodeficiency Syndrome economics, Adult, Employment, Family, Humans, Male, Middle Aged, Self-Help Groups, Sexual Behavior, Sexual Partners, Socioeconomic Factors, Acquired Immunodeficiency Syndrome psychology, Attitude, Truth Disclosure
- Abstract
A questionnaire survey of 103 patients of the Paris Pitié-Salpêtrière Hospital measures the changes in family life, work relations and in sexual behaviour occurring after an HIV infection diagnosis. Most patients choose to keep their diagnosis secret, an attitude that places them into a double bind situation. This silence, chosen as a mean of self-protection, prevents patients from making themselves understood and from mobilising the material and psychological help they need.
- Published
- 1988
44. HIV transmission by oral sex.
- Author
-
Rozenbaum W, Gharakhanian S, Cardon B, Duval E, and Coulaud JP
- Subjects
- Humans, Male, HIV Seropositivity transmission, Sexual Behavior
- Published
- 1988
- Full Text
- View/download PDF
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