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 Conference
"Lifelong treatment of HIV: Challenges and promises"
Dr. Jürgen Rockstroh (biography)
English - 2006-01-20 - 44 minutes
(48 slides)

Summary :
Dr. Rockstroh discusses the challenges in HIV treatment beginning firstly by addressing the noticeable differences in antiretroviral accessibility in low to middle income countries. Sub Saharan Africa remains to be the most affected with the least accessibility to antiretrovirals.

The question of when and how to initiate antiretroviral therapy (ART) is still a debatable one. The International AIDS society has brought forth several recommendations in the last decade, all of which have had their promises and pitfalls. With the extensive list of HIV drugs available, various treatment options are available. Throughout this presentation, Dr. Rockstroh examines many different ART regimens and their toxicities.

It is well know that complications arise from HAART. These include hepatic toxicity, adherence issues, lipodystrophy, gastrointestinal complications, cardiovascular disease, and resistance emergence. Mitochondrial DNA depletion contributing to lipodystrophy was found to vary among NRTI based regimens but is highest with thymidine analogue regimens such as d4T. Fortunately, the MITOX and RAVE studies demonstrate a degree of reversibility of lipoatrophy when switched to abacavir or tenofovir. Dr. Rockstroh introduces an interesting technique to measure lipoatrophy known as surface laser imaging.

Other adverse events include the well defined hypersensitivity reaction (HSR) induced by abacavir which has been linked to a specific HLA allele; the HLA-B*5701. HSR occurs early on in treatment and is independent of dosage, be it a once daily or twice daily regimen. Prospective genetic screening for HLA-B*5701 show promising outcomes in avoiding HSRs in these predisposed individuals.

Cardiovascular disease is another complication of HIV infections and is speculated to be attributed to inflammation which induces alterations in lipid metabolism. It was made apparent by the ABCDE study that HAART regimens show beneficial effects on lipid profiles. It is important to recognize that this varied depending on the backbone regimen administered thus providing a means of controlling for adverse cardiovascular events.

Furthermore, Dr. Rockstroh discusses the current issues surrounding drug resistance and the effectiveness of genotyping prior to initiating ART. Other important matters to consider when choosing ART are pharmacokinetic profiles of drugs, and potential drug/drug interactions. Finally, Dr. Rockstroh concludes by addressing the challenges of Hepatitis C co-infections and the effects of HAART on liver disease progression.

Copyright © 2006 E-MedHosting.com Inc.

Learning objectives :
After viewing this presentation, participants will be able to discuss:
- The epidemiology and accessibility of ART;
- When and how to initiate ART;
- Prevention and management of short and long term toxicities;
- The importance of drug resistance, interactions and pharmacokinetic profiles when choosing an appropriate ART regimen;
- Hepatitis C co-infections.

Bibliographic references :
Charles C. J. Carpenter; Margaret A. Fischl; Scott M. Hammer; Martin S. Hirsch; Donna M. Jacobsen; David A. Katzenstein; Julio S. G. Montaner; Douglas D. Richman; Michael S. Saag; Robert T. Schooley; Melanie A. Thompson; Stefano Vella; Patrick G. Yeni; Paul A. Volberding. Antiretroviral Therapy for HIV Infection in 1998: Updated Recommendations of the International AIDS Society–USA Panel. Journal of the American Medical Association, July 1998. 280(1), 78-86.

Patrick G. Yeni; Scott M. Hammer; Charles C. J. Carpenter; David A. Cooper; Margaret A. Fischl; Jose M. Gatell; Brian G. Gazzard; Martin S. Hirsch; Donna M. Jacobsen; David A. Katzenstein; Julio S. G. Montaner; Douglas D. Richman; Michael S. Saag; Mauro Schechter; Robert T. Schooley; Melanie A. Thompson; Stefano Vella; Paul A. Volberding. Antiretroviral Treatment for Adult HIV Infection in 2002: Updated Recommendations of the International AIDS Society-USA Panel. Journal of the American Medical Association, July 2002. 288(2), 222-235.

Patrick G. Yeni; Scott M. Hammer; Martin S. Hirsch; Michael S. Saag; Mauro Schechter; Charles C. J. Carpenter; Margaret A. Fischl; Jose M. Gatell; Brian G. Gazzard; Donna M. Jacobsen; David A. Katzenstein; Julio S. G. Montaner; Douglas D. Richman; Robert T. Schooley; Melanie A. Thompson; Stefano Vella; Paul A. Volberding. Treatment for Adult HIV Infection: 2004 Recommendations of the International AIDS Society-USA Panel. Journal of the American Medical Association, July 2004. 292(2), 251-265.

Duvivier C et al. Lower rate of virological suppression in naive patients initiating HAART with NRTI-sparing regimen compared to standard NRTI-containing regimen: Results from Hippocampe – ANRS 121 Trial. 10th EACS Dublin, PS1/3.

Rauch A. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV Cohort. 10th EACS Dublin 2005. Abs PS6/2.

Daniel Podzamczer, E Ferrer, P Sanchez, J Gatell, M Crespo, M Lonca, J Sanz, J Niubo, S Veloso, J Llibre, P Barrufet, M Ribas, E Merino, J Martínez-Lacasa, C Alonso-Villaverde, and ABCDE Study Group. A Randomized Comparison between Abacavir and Stavudine, both Combined with Lamivudine/Efavirenz, in Antiretroviral-Naive Patients. Final 96-Week Results of the ABCDE Study. CROI 2005, Boston. Poster 587.

Fisac et al. Abacavir vs d4T: changes in viral load, diabetes, lipids, body changes, cytokines. IAS 2005, Rio de Janeiro. Poster TuPeLB2.2B02.

Graeme J Moyle, MD, MBBS; Edwin DeJesus, MD; Pedro Cahn, MD; Steve A Castillo, MSc; Henry Zhao, PhD; David N Gordon, MB, ChB; Charles Craig, PhD; Trevor R Scott, PhD; for the Ziagen Once-Daily in Antiretroviral Combination Therapy (CNA30021) Study Team. Abacavir Once or Twice Daily Combined With Once-Daily Lamivudine and Efavirenz for the Treatment of Antiretroviral-Naive HIV-Infected Adults: Results of the Ziagen Once Daily in Antiretroviral Combination Study.
JAIDS, April 2005. 38(4), 417-425.

Fiona Lampe, J Gatell, S Staszewski, M Johnson, C Pradier, J Gill, E de Lazzari, B Dauer, M Youle, E Fontas, H Krentz, and A Phillips. Trends Over Time in Initial Virological Failure of First HAART: 1996 to 2002. A Joint Cohort Analysis of 4143 Subjects. CROI 2005, Boston. #593.

A. Phillips, D. Dunn, C. Sabin, A. Pozniak, R. Matthias, A. Geretti, J. Clarke, D. Churchill, I. Williams, T. Hill, H. Green, K. Porter, G. Scullard, M. Johnson, P. Easterbrook, R. Gilson, M. Fisher, C. Loveday, B. Gazzard, D. Pillay. Long term risk of development of drug resistance after starting antiretroviral therapy in routine clinical practice . 7th International Congress on Drug Therapy in HIV Infection. Glasgow, 2004. #PL6.1

Oette M, Kaiser R, Daumer M, Akbari D, Fatkenheuer G, Rockstroh JK, Stechel J, Rieke A, Mauss S, Schmaloer D, Gobels K, Vogt C, Wettstein M, Haussinger D. Primary drug-resistance in HIV-positive patients on initiation of first-line antiretroviral therapy in Germany. European Journal of Medical Research, May 28, 2004. 9(5), 273-8.

Oette M., Kaiser R., Daeumer M., Beerenwinkel N., Petch R., Kroidl A., Hoffmann D., Selbig J., Lengauer T., Haeussinger D., RESINA Study Group. Impact of genotypic HIV drug resistance testing on efficacy of first-line highly active antiretroviral therapy. 10th EACS, Dublin, 2005. PE3.4/9

S Taylor, S Allen, S Fidler, D White, S Gibbons, J Fox, J Clarke, J Weber, P Cane, A Wade, E Smit, and D Back. Stop Study: After Discontinuation of Efavirenz, Plasma Concentrations May Persist for 2 Weeks or Longer. CROI 2004, San Francisco. #131.

Rockstroh JK, Mocroft A, Soriano V, Tural C, Losso MH, Horban A, Kirk O, Phillips A, Ledergerber B, Lundgren J; EuroSIDA Study Group. Influence of Hepatitis C Virus Infection on HIV-1 Disease Progression and Response to Highly Active Antiretroviral Therapy. Journal of Infectious Diseases, 2005. 192(6), 992-1002.

Naztfa Qurishi, Christina Kreuzberg, Guido Lüchters, Wolfgang Effenberger, Bernd Kupfer, Tilman Sauerbruch, Jürgen K Rockstroh and Ulrich Spengler. Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection. The Lancet, November 22, 2003. 362(9397), 1708-1713.

Sulkowski, Mark S a; Mehta, Shruti H; Torbenson, Michael; Afdhal, Nezam H; Mirel, Lisa; Moore, Richard D; Thomas, David L. Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus. AIDS, April 8, 2005. 19(6), 585-592.

Mooser Vincent, Carr Andrew. Antiretroviral therapy-associated hyperlipidaemia in HIV disease. Current Opinion in Lipodology, June 2001. 12(3), 313-9.

Walli RK, Michl GM, Bogner JR, Goebel FD. Improvement of HAART-associated insulin resistance and dyslipidemia after replacement of protease inhibitors with abacavir. European Journal of Medical Research, October 29, 2001. 6(10), 413-421.

Henry Zhao, Jaime Hernandez, Amy Cutrell, Naomi Givens, John Wakeford, Trevor Scott. Safety of abacavir (ABC) + lamivudine (3TC)-based HAART in ART-naïve HIV-infected subjects with and without hepatitis B (HBV) and/or hepatitis C (HCV) co-infection. IAS 2005, Rio de Janeiro. Poster TuPe1.1C16.

Lewden C.1, APROCO-COPILOTE Study Group, Aquitaine Cohort Study Group.
Responders to antiretroviral treatment over 500 CD4/mm3 reach same mortality rates as general population: Aproco and Aquitaine cohorts, France. EACS Dublin, 2005. PE18.4/8.

   


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