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insulin resistance
  Français - August 16, 2011
CMEonHIV.com is dedicated to providing online CME presentations (slides with voiceover) on HIV/AIDS for healthcare professionals given by local and international experts to keep you up-to-date on the ongoing developments in the field.
  Topic  
HIV Related Complications

Viral co-infections notably with HCV and HBV are relatively frequent among HIV infected patients. These represent supplementary factors affecting morbidity and mortality. Successful treatment of these co-infections at the same time as ongoing HIV treatment represents a challenge for clinicians and requires a multidisciplinary collaborative effort. Despite the significant advances in treatment options, opportunistic infections still represent today a major cause of death in patients suffering from HIV. Some of them lead to the development of neoplasias (HPV and anogenital cancer). These infections should therefore be prevented as much as possible (prophylaxis), and when the case arises treated effectively. Patients suffering from HIV are exposed to the risk of lymphomas (non-Hodgkin’s lymphoma (NHL) or Hodgkin’s Disease). With some precautions, chemotherapy can be used in association with antiretroviral therapy.



HIV and the Brain: Optimal Therapy - David Clifford
Neurocognitive Complications of HIV and Their Management - Scott Letendre
New data on immunotherapy for HPV related anal dysplasia in... - Dr. Jonathan Anderson
Discovering the Future: GlaxoSmithKline´s ongoing... - Dr. Lynn Marks
Cardiovascular Risk in HIV Positive Patients - Dr. Marek Smieja
HSV and HIV- A Troublesome Synergy? - Dr. Dr. Robert Patrick O'Brien
In HIV-seropositive men, increased HPV-16 viral loads and... - Julie Fontaine
Genetic polymorphism predisposes to persistence of human... - Simon Gagnon
Persistence of Anal Infection by Human Papillomaviruses... - Dr. François Coutlée
Anal Cancer Screening : An update of the TRACE Study - Dr. Irving Salit
HIV/HCV Co-infection - Dr. Shariq Haider
Opportunistic Infections - Dr. Peter Phillips
Management of Dual HIV/HCV Infection - Dr. Valentina Montessori
Diagnosis and Management of Anal Dysplasia - Dr. Robert Taylor
Hepatitis C and HIV : Current Challenges and Treatment - Dr. Valentina Montessori
New Developments in Opportunistic Infections (OIs) - Dr. Peter Phillips
Hepatitis C and HIV: Current challenges and treatment - Dr. Valentina Montessori
What's New on Opportunistic Infections - Dr. Peter Phillips
Challenges for the management of HIV and Hepatitis C... - Dr. Marina Klein

 Conference 
"HIV and the Brain: Optimal Therapy"
David Clifford (biography)
English - 2009-04-24 - 34 minutes
(60 slides)

Summary :
Since its outbreak, HIV has been associated with neurodegenerative disorders and dementia. With the advent of HAART and successful HIV therapy, almost all of the associated neurological problems have had a very low occurrence in the clinic. Consequently, to carefully look at this issue, the CHARTER study was designed.

In its phase 1A, the CHARTER trial was mainly aimed to look at the patterns of use of antiretroviral therapy and its association with neurocognitive disorders. However, the level of neurocognitive impairment observed in the CHARTER study, was comparable to what has been seen in previous studies, carried out in pre-ARV and pre-HAART eras. It showed that around 50% of the subjects had some degree of cognitive impairment, the majority belonging to the "Mild" group. Further analysis seemed to show that this was not due to confounders (for example drug abuse) but was rather associated with the intrinsic toxicity of the virus towards neurons. As a matter of fact, the copy number of HIV viruses present in the CNS and, by extension, in the brain, could be used as a good indicator.

Because of the presence of the blood-brain barrier, one of problems encountered is to actually deliver the drug to the brain. As shown in animal models and presented by Dr. Clifford, the brain is the part of the body that receives the smallest amount of the active drug. Nonetheless, the association with a high number of viruses present in the CNS and a poor NP score seems to remain true. A randomized controlled trial is presently being designed to look at the association between ARV drug entry in the brain and CPE score.

Learning objectives :
After viewing this presentation, the participant will be able to discuss:
- The nature of neurocognitive disorders associated with HIV
- The epidemiology of neurological disorders associated with HIV
- The current problems with treating neurocognitive HIV-associated disorders

Bibliographic references :
Palella, Frank J. Jr MD; Baker, Rose K. MA; Moorman, Anne C. BSN, MPH; Chmiel, Joan S. PhD; Wood, Kathleen C. BSN; Brooks, John T. MD; Holmberg, Scott D. MD, MPH; HIV Outpatient Study Investigators Mortality in the Highly Active Antiretroviral Therapy Era: Changing Causes of Death and Disease in the HIV Outpatient Study J Acquir Immune Defic Syndr. 2006 Sep;43(1):27-34.

Scott Letendre, MD and al.; for the CHARTER Group Validation of the CNS Penetration-Effectiveness Rank for Quantifying Antiretroviral Penetration Into the Central Nervous System Arch Neurol. 2008;65(1):65-70.

A. Antinori and al. Updated research nosology for HIV-associated neurocognitive disorders Neurology, Oct 2007; 69: 1789 - 1799.

   


 Conference 
"Neurocognitive Complications of HIV and Their Management"
Scott Letendre (biography)
English - 2009-03-11 - 47 minutes
(34 slides)

Summary :
HIV-associated neurocognitive disorders (HAND) have no pre-existing cause, they should follow infection with HIV, says Dr. Letendre.

These disorders affect daily functioning to different degrees. Asymptomatic neurocognitive impairment (ANI) is associated with no dysfunction, and mild neurocognitive disorder (MND) and HIV-associated dementia (HAD) with mild and marked impairment respectively.

The CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study, funded by the NIH, enrolled over 1500 people in the U.S. The study found that impaired global neuropsychological performance is common in HIV, and has provided data on risk factors for HAND.

Antiretrovirals reduce HIV replication in the central nervous system (CNS), and this is considered necessary but not always sufficient for improving cognition, says Dr. Letendre. Individuals with lower CD4 nadirs or HAND may need better penetrating antiretrovirals and possibly adjunctive therapy for cognition to be maintained or improved.

Apart from the physicochemical characteristics of these drugs for understanding whether they reach therapeutic concentrations in the CNS, there is the concentration of drug in the CSF relative to the IC50. Dr. Letendre shows pharmacokinetic data for abacavir, tenofovir, amprenavir and atazanavir.

Dr. Letendre shows analyses from CHARTER study participants, utilising physicochemical, pharmacokinetic and pharmacodynamic data to estimate the penetration of different antiretroviral regimens in the CNS, and comparing these scores to actual viral loads in the CSF.

Copyright © 2009 MULTIWEBCAST "State-of-the-Art Webcast Services"

Learning objectives :
After viewing this presentation the participant will be able to discuss:
- Neurocognitive findings from the CHARTER study
- Risk factors for HIV-associated neurocognitive disorders
- Physicochemical characteristics, pharmacokinetic and pharmacodynamic data for different ARVs in the CNS
- Estimated ARV regimen CNS penetration compared to CNS viral loads

Bibliographic references :
A. Antinori, MD, G. Arendt, MD, J. T. Becker, PhD, B. J. Brew, MBBS, MD, FRACP, D. A. Byrd, PhD, M. Cherner, PhD, D. B. Clifford, MD, P. Cinque, MD, PhD, L. G. Epstein, MD, K. Goodkin, MD, PhD, M. Gisslen, MD, PhD, I. Grant, MD, R. K. Heaton, PhD, J. Joseph, PhD, K. Marder, MD, MPH, C. M. Marra, MD, J. C. McArthur, MBBS, MPH, M. Nunn, PhD, R. W. Price, MD, L. Pulliam, PhD, K. R. Robertson, PhD, N. Sacktor, MD, V. Valcour, MD and V. E. Wojna, MD Updated research nosology for HIV-associated neurocognitive disorders NEUROLOGY 2007;69:1789-1799

Scott Letendre, MD; Jennifer Marquie-Beck, BS; Edmund Capparelli, PharmD; Brookie Best, PharmD; David Clifford, MD; Ann C. Collier, MD; Benjamin B. Gelman, MD, PhD; Justin C. McArthur, MPH, MBBS; J. Allen McCutchan, MD; Susan Morgello, MD; David Simpson, MD; Igor Grant, MD; Ronald J. Ellis, MD, PhD; for the CHARTER Group Validation of the CNS Penetration-Effectiveness Rank for Quantifying Antiretroviral Penetration Into the Central Nervous System Arch Neurol. 2008;65(1):65-70.

   


 Conference 
"New data on immunotherapy for HPV related anal dysplasia in people with HIV"
Dr. Jonathan Anderson (biography)
English - 2007-08-15 - 29 minutes
(35 slides)

Summary :
In this presentation Dr. Anderson presents findings from a Phase Ib randomised, placebo-controlled, dose-escalation study to determine the safety, tolerability and immunogenicity of an HPV-16 therapeutic vaccine in HIV-positive participants with oncogenic HPV infection of the anus.

High-grade anal intraepithelial neoplasia (AIN) is a growing problem amongst HIV positive men having sex with men (MSM), for which there are no clear evidence-based therapeutic options at present. Oncogenic types of Human Papillomavirus (HPV), particularly types 16 and 18, have been implicated in the pathogenesis of AIN and also anal cancer. In the natural history, there is transition of high-grade AIN to anal cancer, however the rate of progression is unclear.

The current treatments for AIN include local treatments and surgery. The immunomodulator imiquimod has been used as well, and it has been postulated that a therapuetic vaccine can be used.

In the present study described by Dr. Anderson, there were 35 participants - all MSMs, 33 of whom completed the study. The subjects were HIV-positive and most were on antiretroviral therapy. All had documented anal infection with oncogenic HPV.

The study results demonstrate that the novel immunotherapeutic HPV-16 E6E7 ISCOMATRIX® vaccine is safe and well-tolerated. Dr. Anderson describes the immune responses which persisted out to Day 252 despite previous severe immunosuppression; the lack of impact on HPV-16 viral load; the risk of new infections; the overall value of the study and remaining issues regarding screening and treatment of AIN.

Copyright © 2008 MULTIWEBCAST "State-of-the-Art Webcast Services"

Learning objectives :
After viewing this presentation the participant will be able to discuss:

- Anal intraepithelial neoplasia – diagnosis; current treatments; issues with screening
- Safety and tolerability of a novel HPV-16 immunotherapeutic agent in HIV+ MSMs with oncogenic HPV infection of the anus

   


 Conference 
"Discovering the Future: GlaxoSmithKline´s ongoing commitment to new antiretroviral development"
Dr. Lynn Marks (biography)
English - 2005-11-19 - 28 minutes
(24 slides)

Summary :
GlaxoSmithKline (GSK) has maintained its leadership position in the treatment of HIV/AIDS since the introduction of Retrovir® (zidovudine, AZT), the first antiretroviral drug to be approved for the treatment of HIV infection, in April 1987. GSK currently has eight antiretroviral products approved for the treatment of HIV in the European Union.

Despite the availability of 20 antiretroviral products in the market place, we are faced with a global HIV/AIDS pandemic for which there is no imminent cure. The growing problem of viral resistance to the existing anti-HIV drugs has resulted in an unmet need for improved therapies to treat HIV infection in the developed world. In the developing world the pressing need is for access to optimum healthcare in addition to the availability of antiretroviral therapy.

GSK has two approaches to address the issue of drug resistance. Firstly, GSK is committed to developing next generation drugs within the existing drug classes that are both highly effective against resistant strains of HIV, and have a better safety and tolerability profile. Secondly, GSK has active drug discovery programs that are investigating novel targets as a means of controlling replication of the virus.

GSK is also committed to playing a full part in addressing the challenges of the developing world by taking an innovative, responsible and, importantly, sustainable approach aimed at improving the lives of people living with HIV/AIDS. GSK’s commitment and contribution are focussed on five key areas:

• investment in research and development into new drugs and vaccines
• clinical trials focusing on the needs of the developing world
• preferential pricing on our antiretrovirals to a wide range of customers in the world’s poorest countries
• community investment activities and partnerships that foster effective approaches against the disease and the challenges it presents
• innovative partnerships and solutions

For more than fifteen years, GSK products have formed the core of HIV/AIDS treatment guidelines around the world. As we look to the future, GSK remains committed to excellence in the care of individuals with HIV infection.

   


 Conference 
"Cardiovascular Risk in HIV Positive Patients"
Dr. Marek Smieja (biography)
English - 2005-09-08 - 46 minutes
(47 slides)

Summary :
Several studies have associated HIV infection with an increased cardiovascular risk. In this presentation, Dr. Smieja addresses the possibility of HIV as a risk factor of cardiovascular disease in itself. As well, he looks at the effect of HIV treatment in predisposing a patient to increased cardiovascular risk.

Is HIV a risk factor for cardiovascular disease? It is important to identify the prevalence of common risk factors in HIV positive patients such as age, gender, cholesterol, diabetes, etc so as to determine whether it is the infection or other accompanying risk factors involved. Dr. Smieja reviews several studies looking specifically at common cardiovascular risk factors among HIV positive patients.

Is the HIV treatment a risk factor for cardiovascular disease? It is important to recognize that an increase in risk due to HIV treatment may not necessarily encourage the discontinuation of treatment. One must take into consideration that in doing so, most probably will exacerbate the infection leading to other more severe outcomes. Dr. Smieja presents studies on the incidence of cardiovascular events in patients on HAART therapy. He introduces several measuring techniques useful in identifying those at risk of cardiovascular disease. These include exercise stress testing, coronary angiography, coronary artery CT, brachial artery ultrasound, and carotid artery ultrasound.

Overall, Dr. Smieja delivers an in depth review of past and current studies on HIV infection and treatment in cardiovascular risk and concludes by stating future directions.

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Learning objectives :
After viewing this presentation, participants will be able to discuss:
- HIV infection as a risk factor for cardiovascular disease;
- HIV treatment as a risk factor for cardiovascular disease;
- Results from the following studies:
o The Data Collection on Adverse Events of Anti-Viral Drugs Study (D:A:D)
o Canadian HIV Vascular Study
o The San Francisco Ultrasound Study
o The Veterans Affairs Study

Bibliographic references :
Annika Rosengren, Steven Hawken, Stephanie Ôunpuu, Karen Sliwa, Mohammad Zubaid, Wael A Almahmeed, Kathleen Ngu Blackett, Chitr Sitthi-amorn, Hiroshi Sato, Salim Yusuf and for the INTERHEART investigatorsAssociation of psychosocial risk factors with risk of acute myocardial infarction in 11 119 cases and 13 648 controls from 52 countries (the INTERHEART study): case-control study The Lancet, Volume 364, Issue 9438, 11 September 2004-17 September 2004, Pages 953-962

Philip Greenland; Laurie LaBree; Stanley P. Azen; Terence M. Doherty; Robert C. DetranoCoronary Artery Calcium Score Combined With Framingham Score for Risk Prediction in Asymptomatic IndividualsJAMA, January 14, 2004; 291: 210 - 215

Priscilla Y. Hsue, Joan C. Lo, Arlana Franklin, Ann F. Bolger, Jeffrey N. Martin, Steven G. Deeks, and David D. WatersProgression of Atherosclerosis as Assessed by Carotid Intima-Media Thickness in Patients With HIV InfectionCirculation, Apr 2004; 109: 1603 - 1608.

   


 Conference 
"HSV and HIV- A Troublesome Synergy?"
Dr. Dr. Robert Patrick O'Brien (biography)
English - 2004-06-28 - 36 minutes
(36 slides)

Summary :
In this presentation, Dr. O’Brien takes a look at the increasingly recognized problem presented by HSV/HIV co-infection. HSV infection is one of the most common sexually transmitted illnesses in the world. 20% to 25% of the North American population is infected. Men who have sex with men (MSM) have a higher rate of HSV infection (50% in non-HIV-infected persons) and this rate is increased even further in HIV-infected MSM. Moreover, an increasing amount of genital herpes is due to HSV-1 infection, especially among MSM.

Genital herpes is underdiagnosed, according to Dr. O’Brien, in part because the majority of cases are either asymptomatic or present with atypical symptoms.

Dr. O’Brien reveals how HSV infection acts as a cofactor for HIV transmission, acquisition and progression. HIV effects on the natural history of HSV infection are also discussed.

In this presentation, the relative benefits and draw-backs of different HSV diagnostic modalities are presented as well as the treatment options for HSV alone and HSV in the setting of HIV co-infection.

Dr. O’Brien concludes his talk with a discussion of the potential benefits of treating HSV infection in both HIV+ and HIV- individuals and the need for objective data to support these theoretical advantages.

Copyright © 2004 MULTIWEBCAST "State-of-the-Art Webcast Services"

Learning objectives :
After viewing this presentation, participants will be able to discuss:
- The magnitude of the Genital Herpes epidemic in the North America.
- The role of HSV in potentiating the transmission, acquisition, and progression of HIV.
- The role of HIV in promoting the spread of HSV and in altering its Natural History.
- The potential benefit to both HIV-infected and non-infected individuals of treating HSV infection and the evidence for these.

Bibliographic references :
Corey L, Handsfield HH.Genital herpes and public health: addressing a global problemJAMA. 2000 Feb 9;283(6):791-4.

Gottlieb SL, Douglas JM Jr, Schmid DS, Bolan G, Iatesta M, Malotte CK, Zenilman J, Foster M, Baron AE, Steiner JF, Peterman TA, Kamb ML; Project RESPECT Study Group.Seroprevalence and correlates of herpes simplex virus type 2 infection in five sexually transmitted-disease clinics.J Infect Dis. 2002 Nov 15;186(10):1381-9. Epub 2002 Oct 23.

Lafferty WE, Downey L, Celum C, Wald A.Herpes simplex virus type 1 as a cause of genital herpes: impact on surveillance and prevention.J Infect Dis. 2000 Apr;181(4):1454-7. Epub 2000 Apr 13.

Holmberg SD, Stewart JA, Gerber AR, Byers RH, Lee FK, O'Malley PM, Nahmias AJ.Prior herpes simplex virus type 2 infection as a risk factor for HIV infection.JAMA. 1988 Feb 19;259(7):1048-50.

Schacker T. The role of HSV in the transmission and progression of HIV. Herpes. 2001 Jul;8(2):46-9.

Schacker T, Ryncarz AJ, Goddard J, Diem K, Shaughnessy M, Corey L. Frequent recovery of HIV-1 from genital herpes simplex virus lesions in HIV-1-infected men. JAMA. 1998 Jul 1;280(1):61-6.

Augenbraun M, Feldman J, Chirgwin K, Zenilman J, Clarke L, DeHovitz J, Landesman S, Minkoff H.Increased genital shedding of herpes simplex virus type 2 in HIV-seropositive women.Ann Intern Med. 1995 Dec 1;123(11):845-7.

Wald A, Link K.Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis.J Infect Dis. 2002 Jan 1;185(1):45-52. Epub 2001 Dec 14.

Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, vanCott T, Quinn TC; Rakai Project Team.Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda.Lancet. 2001 Apr 14;357(9263):1149-53.

Wald A.New therapies and prevention strategies for genital herpes.Clin Infect Dis. 1999 Jan;28 Suppl 1:S4-13.

Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, Tyring S, Douglas JM Jr, Corey L.Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women.JAMA. 2001 Jun 27;285(24):3100-6.

Corey L, Wald A, Patel R, Sacks SL, Tyring SK, Warren T, Douglas JM Jr, Paavonen J, Morrow RA, Beutner KR, Stratchounsky LS, Mertz G, Keene ON, Watson HA, Tait D, Vargas-Cortes M; Valacyclovir HSV Transmission Study Group.Once-daily valacyclovir to reduce the risk of transmission of genital herpes.N Engl J Med. 2004 Jan 1;350(1):11-20.

Schacker T, Zeh J, Hu H, Shaughnessy M, Corey L.Changes in Plasma Human Immunodeficiency Virus Type 1 RNA Associated with Herpes Simplex Virus Reactivation and Suppression J Infect Dis. 2002 Dec 15;186(12):1718-25. Epub 2002 Nov 22.

DeJesus E, Wald A, Warren T, Schacker TW, Trottier S, Shahmanesh M, Hill JL, Brennan CA; Valacyclovir International HSV Study Group.Valacyclovir for the suppression of recurrent genital herpes in human immunodeficiency virus-infected subjects.J Infect Dis. 2003 Oct 1;188(7):1009-16. Epub 2003 Sep 10.


Additional references of interest

Posavad CM, Wald A, Kuntz S, Huang ML, Selke S, Krantz E, Corey L. Frequent reactivation of herpes simplex virus among HIV-1-infected patients treated with highly active antiretroviral therapy. J Infect Dis. 2004 Aug 15;190(4):693-6. Epub 2004 Jul 13.

Mostad SB, Kreiss JK, Ryncarz A, Chohan B, Mandaliya K, Ndinya-Achola J, Bwayo JJ, Corey L.Cervical shedding of herpes simplex virus and cytomegalovirus throughout the menstrual cycle in women infected with human immunodeficiency virus type 1.Am J Obstet Gynecol. 2000 Oct;183(4):948-55.

Wald A, Huang ML, Carrell D, Selke S, Corey L. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis. 2003 Nov 1;188(9):1345-51. Epub 2003 Oct 31.

Wald A, Corey L.How does herpes simplex virus type 2 influence human immunodeficiency virus infection and pathogenesis?J Infect Dis. 2003 May 15;187(10):1509-12.

   


 Conference 
"In HIV-seropositive men, increased HPV-16 viral loads and HPV-16 integrated forms are associated with anal intraepithelial lesions"
Julie Fontaine (biography)
English - 2004-05-14 - 13 minutes
(22 slides)

   


 Conference 
"Genetic polymorphism predisposes to persistence of human papillomavirus types 33 and 35 in HIV-infected women"
Simon Gagnon (biography)
English - 2004-05-14 - 12 minutes
(19 slides)

Bibliographic references :
Simon Gagnon, Catherine Hankins, Cécile Tremblay, Karina Pourreaux, Pierre Forest, Fabrice Rouah, The Canadian Women's HIV Study Group, François Coutlée Polymorphism of human papillomavirus type 31 isolates infecting the genital tract of HIV-seropositive and HIV-seronegative women at risk for HIV infection J Med Virol. 2005 Feb;75(2):213-21.

   


 Conference 
"Persistence of Anal Infection by Human Papillomaviruses (HPV) and Anal Disease in HIV-Seropositive Men"
Dr. François Coutlée (biography)
English - 2004-05-14 - 15 minutes
(21 slides)

   


 Conference 
"Anal Cancer Screening : An update of the TRACE Study"
Dr. Irving Salit (biography)
English - 2004-05-13 - 17 minutes
(31 slides)

   


 Conference 
"HIV/HCV Co-infection"
Dr. Shariq Haider (biography)
English - 2003-11-11 - 10 minutes
(4 slides)

Summary :
Although the EUROSIDA Study showed no role of HCV in accelerating the progression of AIDS, there was a rise observed in liver related deaths in HIV/HCV co-infected patients. Clinical data on peg alpha 2a plus Ribavirin (PRESCO Study), and peg alpha 2b plus Ribavirin (Santos et al) in treatment of HIV/HCV co-infected patients will be discussed here, as well as new information on toxicities associated with IFN or peg-IFN plus Ribavirin (Laguno et al), and finally barriers to treatment of HIV/HCV co-infected patients (Benta et al).

Copyright © 2004 MULTIWEBCAST "State-of-the-Art Webcast Services"

Learning objectives :
The participant will learn about new data from the EUROSIDA Study, clinical data on peg alpha 2a and peg alpha 2b, toxicities and side effects of therapy using interferon or pegylated interferon with ribavirin, and barriers to HIV/HCV co-infection treatment.

   


 Conference 
"Opportunistic Infections"
Dr. Peter Phillips (biography)
English - 2003-03-30 - 37 minutes
(46 slides)
(3 questions)

Summary :
Immune Reconstitution Disease (IRD). Since the availability of highly active antiretroviral therapy, an increasing number of opportunistic pathogens have been associated with a wide range of IRDs. The severity ranges from life threatening inflammatory reactions (e.g progressive multifocal leukoencephalopathy, pCP, cryptococcal meningitis) to more benign conditions such as herpes zoster infection. Other HIV-associated conditions which have been described in the context of IRD include tuberculosis, MAC, CMV, hepatitis B and C and histoplasmosis. Occasionally non-infectious autoimmune diseases may also be exacerbated by HAART-induced immune reconstitution, including Graves’ disease, autoimmune thyroiditis, and SLE. Occasional IRD syndromes have also been described in patients with lymphoma, Kaposi’s sarcome, Castleman’s disease and sarcoid-like disorders.
A definitive diagnosis may be possible in some cases, but only suspected in others. For example, in tuberculous IRD, the TB diagnosis typically preceded the initiation of antiretrovirals, and the diagnosis of MTb-IRD is one of exclusion. In contrast, for MAC-Related IRD, the HAART regimen usually unmasks subclinical MAC and a definitive diagnosis can be established by isolating the organism from a normally sterile site. The diagnosis of HIV-related IRD generally rests upon the following: a) the finding of a localized inflammatory process; and b) smear or culture positive for the opportunistic pathogen; and c) evidence of immune reconstitution (increase in CD4 cell count and often a shift toward a histologic tissue reaction more consistent with intact cell mediated immunity, e.g. necrotizing granulomas in mycobacterial infection). Clinical featured of the IRDs are often atypical compared to the classic description of the infections in the pre-HAART era. Althought the majority of these problems deelop witin the first few months of initiating (or revising) an antiretroviral regimen, such reactions have been well described up to a year or more following the initiation of HAART.

Mild IRDmay not require any therapy. Most patients are treated with antimicrobials specific for the responsible pathogen, however the efficacy of such therapies in these settings has not been established. Anecdotal reports suggest a role a systemic corticosteroids in those patients with more severe or persistent inflammatory reactions. Antiretroviral therapy should not be interrupted unless the IRD episode is considered to be life-threatening. Effective prevention strategies for IRS have not been determined. Azithromycin prophylaxis does not appear to prevent MAC-IRD. In order to minimize uncertainty regarding the cause of fevers or inflammatory reactions, it has been recommended that HAART therapy be postponed for 1 to 2 months after the initiation of antituberculous therapy in patients with newly diagnosed TB. A similar recommendation may apply to other opportunistic diseases. The natural course of MAC-IRD included the gradual resolution of symptoms and signs over weeks or months as observed in a small number of patients who have declined specific antimicrobial therapy. IRS should be considered in the differential diagnosis of problems developing within a year or more of initiating or revising HAART.


   


 Conference 
"Management of Dual HIV/HCV Infection"
Dr. Valentina Montessori (biography)
English - 2003-03-30 - 31 minutes
(32 slides)
(6 questions)

Summary :
HIV and Hepatitis C Co-Infection: Current Challenges and Treatment.
Dual infection with both Hum Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) has emerged as an aggressive health threat in marginalized populations. Dually infected patients are not only more likely to suffer from adverse effects from their antiretroviral therapy, but also appear to experience more rapid progression of HCV to cirrhosis and end stage liver disease. HCV Infection has been noted to perhaps diminish CD4 cell improvements with antiretroviral therapy and dually infected patients have been shown to have a more rapid progression to AIDS and death than those with HIV alone. Many factors appear to influence the natural history of liver disease in co infection including exposure to other hepatoxic agents (alcohol, antiretrovirals), or perhaps immune reconstitution with anti-HIV therapy and restoration of anti-HCV immune response.
Historically, HCV/HIV co infection has primarily occurred in patients with congenital coagulation defects through the administration of contaminated blood products. Increasingly, however, needle sharing during drug use (IDU) has been responsible for the spread of infection. The prevalence of HCV in HIV-Infected IDU now approaches 90%. Sexual transmission of HCV may also play a role. Testing for HCV may be misleading. Case reports of false negative HCV antibody testing in HIV-infected individuals with low CD4 cell counts are emerging. There appears to be a role for HCV RNA testing for HCV-antibody negative patients at risk for HCV.

The standard treatments for HCV infection are rapidly evolving. Current treatment strategies include interferon (IFN) plus other antiviral agents such as ribavirin (RBV). Combination therapies produce sustained virologic response rates in 30-35% of cases. IDU are generally considered unlikely to tolerate and adhere to the necessary treatment programs and may require alternative approaches to clinical management. The newer pegylated interferon, which require only one weekly administration, may contribute to successful therapy in this challenging treatment group. Despite recent improvements in treatments for hepatitis, up to 40% of co infected patients are dying from liver disease. Liver transplant has been attempted at some research centres and may be successful in select individuals.
The effect of antiretroviral therapy on hepatic pathology has not been well studied. Similarly, the importance of liver biopsy in evaluation for possible anti-HCV therapy remains a focus for debate. A better understanding of HIV/HCV pathogenesis and treatment options in co-infection is needed if we are to significantly reduce related morbidity and mortality among marginalized populations.


   


 Conference 
"Diagnosis and Management of Anal Dysplasia"
Dr. Robert Taylor (biography)
English - 2003-03-30 - 33 minutes
(24 slides)
(5 questions)

Summary :
Extent of the problem
It is only in recent years that the problem of anal dysplasia has come to the fore. Both underlying HPV infection and immunosuppression are factors in this rise of importance. Anal dysplasia can be classified as low grade or high grade. Although there are not yet conclusive studies, there is mounting evidence that high grade anal dysplasia is a precursor to anal cancer, in the same way that the comparable lesion in the cervix is a known precursor to cervical cancer. Certainly, there is evidence that the incidence of anal cancer among high-risk groups, including persons with HIV, is significantly higher than in the general population.

Those at Risk
Knowing of the role of both HPV infection and immunosuppression in the development of anal dysplasia, the groups at risk are not surprising: persons with HIV, persons who have practiced anal receptive intercourse, persons with anal condylomata acuminata, persons who are recipients of organ transplantation, women who have been diagnosed with cervical cancer or high grade dysplasia.

Methods of Diagnosis
An Awareness of persons at risk is the first step. Condylomata or persistant symptoms may draw attention to the area but a routine anorectal exam, even by those experienced in doing it, will not pick up anal dysplasia. It requires special techniques. The first of these is screening cytology. As in cervical PAP smears, anal cytology smears reveal underlying dysplasia. For positive screens the next step is high resolution anoscopy (HRA) with biopsy of visualized lesions. Most of these lesions in the anus are only viable with HRA magnification after chemical staining (acetic acid, Lugol’s solution). This requires a dedicated set-up and experience. Biopsy confirms the diagnosis and grades it.

Management
Management depends upon the characteristics of the lesion: size (<1 cm larger, or extensive), grade (low or high), location (perianal or anal canal) and presence of symptoms (bleeding, pain, pruritis). When to treat, modality options and follow-up protocol was presented during the talk.


   


 Conference 
"Hepatitis C and HIV : Current Challenges and Treatment"
Dr. Valentina Montessori (biography)
English - 2002-04-15 - 31 minutes
(34 slides)
(4 questions)

Summary :
Dual infection with both Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) has emerged as an aggressive health threat in marginalized populations. Dually infected patients are not only more likely to suffer from adverse effects from their antiretroviral therapy, but also appear to experience more rapid progression of HCV to cirrhosis and end stage liver disease. HCV infection has been noted to perhaps diminish CD4 cell improvements with antiretroviral therapy and dually infected patients have been shown to have a more rapid progression to AIDS and death than those with HIV alone. Many factors appear to influence the natural history of liver disease in coinfection including exposure to other hepatotoxic agents (alcohol), or perhaps immune reconstitution with anti-HIV therapy and restoration of anti-HCV immune response.

Historically, HCV/HIV coinfection has primarily occurred in patients with congenital coagulation defects through the
administration of contaminated blood products. Increasingly, however, needle sharing during injection drug use (IDU) has been
responsible for the spread of infection. The prevalence of HCV in HIV-infected IDU now approaches 90%. Sexual transmission of HCV may also play a role. Testing for HCV may be misleading. Case reports of false negative HCV antibody testing in HIV-infected individuals with low CD4 cell counts are emerging. There appears to be a role for HCV RNA testing for HCV-antibody negative patients at risk for HCV.

The standard treatments for HCV infection are rapidly evolving. Current treatment strategies include interferon (IFN) plus other antiviral agents such as ribavirin (RBV). Combination therapies produce sustained virologic response rates in 30–35% of cases. Despite recent improvements in treatments for hepatitis, IDU are generally considered unlikely to tolerate and adhere to the necessary treatment programs and may require alternative approaches to clinical management. The newer pegylated
interferons, which require only once weekly administration, may contribute to successful therapy in this challenging treatment
group. A better understanding of HIV/HCV pathogenesis and treatment options in co-infection is needed if we are to significantly reduce related morbidity and mortality among marginalized populations.

   


 Conference 
"New Developments in Opportunistic Infections (OIs)"
Dr. Peter Phillips (biography)
English - 2002-04-15 - 10 minutes
(24 slides)
(5 questions)

Summary :
Opportunistic infections (OIs) continue to account for significant morbidity and mortality among HIV-infected individuals who either do not respond to or cannot adhere to highly active antiretroviral therapy. New recommendations for preventive immunization strategies include limiting the use of pneumococcal vaccine to those who are most likely to benefit (i.e. CD4 counts are > 200/mm). Hepatitis A vaccine is recommended for those at increased risk (e.g. IDU, MSM) or with chronic liver disease, including hepatitis B or C.

The short course 2 month tuberculosis prophylactic regimen of pyrazinamide and rifampin has occasionally been associated with severe or fatal hepatitis. Consequently, this pyrazinamide-containing regimen is reserved for those patients who seem unlikely to complete the longer 4 month rifamycin or 9 month INH regimens. Increased utilization of rapid diagnostic tests for tuberculosis (e.g. DNA and RNA probes) may help identify sputum smear-negative cases (22% as likely as smear-positive cases to transmit tuberculosis) and thereby facilitate infection control measures and initiation of therapy. Antimycobacterial therapy is complicated by numerous drug interactions, particularly for the rifamycins (with protease inhibitors and NNRTIs) and clarithromycin (with efavirenz). The efficacy of the 6 month tuberculosis treatment regimen for HIV-infected patients remains uncertain and appears to be associated with a higher relapse rate compared to HIV-negative individuals. Some additional therapeutic options are now available for the management of certain OIs including: cytomegalovirus retinitis (valganciclovir); progressive multifocal leukoencephalopathy (PML) (cidofovir); cryptococcal meningitis (liposomal amphotericin B); esophageal candidiasis (caspofungin); and cryptosporidiosis (nitazoxanide; expanded access in USA). Partial immune reconstitution associated with HAART has been associated with atypical manifestations of various Ois, particularly MAC (localized lymphadenitis), tuberculosis (paradoxical reactions), and CMV retinitis (vitritis). The spectrum of immune reconstitution disease continues to expand. Partial immune reconstitution has also allowed the safe discontinuation of primary prophylaxis for MAC (if CD4 >100/mm3 ), PCP and toxoplasmosis (if CD4 >200/mm3). Similarly, longterm suppressive therapy (secondary prophylaxis) can be safely discontinued for PCP (if CD4 >200/mm3 ). There also appears to be a low risk of recurrence after discontinuing suppressive therapy for selected patients with CMV retinitis or toxoplasmosis (if CD4 >100-150/mm3), MAC (if CD4 >100/mm3 ), and cryptococcosis (if CD4 >100-200/mm3).

   


 Conference 
"Hepatitis C and HIV: Current challenges and treatment"
Dr. Valentina Montessori (biography)
English - 2001-04-24 - 70 minutes
(49 slides)

   


 Conference 
"What's New on Opportunistic Infections"
Dr. Peter Phillips (biography)
English - 2001-04-24 - 39 minutes
(29 slides)
(22 slides)

   


 Conference 
"Challenges for the management of HIV and Hepatitis C Co-infection"
Dr. Marina Klein (biography)
English - 2000-12-15 - 47 minutes
(40 slides)

   


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