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Talk on HIV infection
tumalapalli venkateswara rao
, Professor
Travancore Medical College, Kollam Kerala
Published on
May 04, 2011
Talk on HIV infection
Published in:
Health & Medicine
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Trainer Notes: Using the contents in the graph, mention that Triple drug anti retroviral therapy is required for achieving the end point of maximal and durable viral suppression. Also it is important to remember that the suppression is maximal and also durable, meaning the suppression should be long lasting. Mention the ineffectiveness of mono therapy and dual therapy in suppressing the viral load effectively for a long duration.
Trainer Notes: Inform the participants about the historical facts on ART (HAART: Highly Active Antiretroviral Therapy)
Step 2: Goals of ART and the relevance of Triple drug therapy (Slides 3-8) – 5 minutes Trainer Notes: Relate the questions from the case study slide to the information on this slide. Mention the participants that Ms. Jyothi's photos were taken before ART and after ART within the duration of 1 year . Request the participants to see the "Jyoti's Hope video" during the training programme Reader Notes: ART, anti retroviral therapy, is a combination of at least three drugs, with representation from at least 2 classes of the drugs. This is required for achieving the end point of maximal and durable viral suppression. It is important to remember that the suppression should be maximal, preferably below the level of detection of current testing kits, and also durable, meaning the suppression should be long lasting. By achieving this, we can prevent the emergence of drug resistant mutants. Once viral suppression is achieved, the body's immune system improves, as reflected by an improved survival and quality of life
Step 3: ART Initiation: When to start (Slides 9- 13) - 8 minutes Trainer Notes: Explain the need to have a guideline for the initiation of ART in the national programme using the contents in the slide Regarding the 3 rd point, whether ART need to be initiated in patients with more than 500 CD4 cell count, the trainer may use the following details to explain to the participants. As per the DHHS guideline, for patients with CD4 counts > 500 cells/mm 3 , 50% of the Panel members favour starting antiretroviral therapy (B); the other 50% of members view treatment is optional (C) in this setting (B/C-III) . What is 'B' and 'C' Rating?? Strength of Recommendation A: Strong recommendation for the statement B: Moderate recommendation for the statement C: Optional recommendation for the statement Quality of Evidence for Recommendation I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints II: One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes III: Expert opinion Ref: Zolopa A, Andersen J, Powderly W, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One. 2009;4(5):e5575.
Trainer Notes: Explain the National guideline using the contents in Table.
Step 3: WHO Clinical Staging of HIV infection (Slides 14-20) - 10 minutes Trainer Notes: Refer to Handout on WHO Clinical Staging in the Participant Manual Discuss WHO Clinical staging 1
Trainer Notes: Refer to Handout on WHO Clinical Staging in the Participant Manual Discuss WHO Clinical staging 2
Trainer Notes: Refer to Handout on WHO Clinical Staging in the Participant Manual Discuss WHO Clinical staging 3
Trainer Notes: Refer to Handout on WHO Clinical Staging in the Participant Manual Discuss WHO Clinical staging 3 (continued)
Trainer Notes: Refer to Handout on WHO Clinical Staging in the Participant Manual Discuss WHO Clinical staging 4
Trainer Notes: Refer to Handout on WHO Clinical Staging in the Participant Manual Discuss WHO Clinical staging 4 (Continued)
Trainer Notes: Refer to Handout on WHO Clinical Staging in the Participant Manual Discuss WHO Clinical staging 4 (Continued)
Trainer Notes: Trainer has to elaborate Service Delivery under care and support activities of NACP III
Trainer Notes: In 2008, Centres of Excellence were identified to serve as models in HIV/AIDS care and support and to provide high quality comprehensive care for persons affected by HIV/AIDS. Identifying the need for a multi-factorial approach to the care of patients affected by HIV and issues surrounding long term adherence, there was a need to shift to a chronic patient management approach. Constant changes in patient management and treatment and the profile of HIV drug resistance requires ongoing training and upgrading of knowledge and skills among health care providers. These centres need to carry out operational research that contributes to programme management and policy making. Institutions selected as Centres of Excellence were medical colleges of high technical repute and willing to provide dedicated staff, infrastructure and technical support towards the programme. Ten such centres were identified that have been providing ART care, support and treatment and in varying capacities involved in training and research.
Trainer Notes: The current functional Centres of Excellence in HIV/ AIDS that have been established are in the following medical institutions: Government Gandhi General Hospital , Hyderabad, Andhra Pradesh Post Graduate Institute of Medical Education & Research (PGIMER) , Chandigarh Maulana Azad Medical College (MAMC), New Delhi Bairamji Jijibhai Medical College (BJMC), Ahmedabad, Gujarat Bowring and Lady Curzon Hospital, Bangalore, Karnataka Calcutta School of Tropical Medicine, Kolkata, West Bengal Sir J.J. Hospital, Mumbai, Maharashtra Government Hospital of Thoracic Medicine (GHTM), Tambaram , Chennai, Tamil Nadu Banaras Hindu University, Varanasi, Uttar Pradesh Regional Institute of Medical Sciences (RIMS), Imphal, Manipur
Trainer Notes: Discuss the Centres of Excellence under the national programme and their designated ART centres Source: National Guidelines on Second-line ART for adults and adolescents, November 2008; page 71-72
Trainer Notes: Discuss the Centres of Excellence under the national programme and their designated ART centres Source: National Guidelines on Second-line ART for adults and adolescents, November 2008; page 71-72
Trainer Notes: Patients experiencing treatment failure with first line ART are referred to the Centres of Excellence for further evaluation and second line treatment, if required. However, many patients are reportedly facing problems due to long travel distance, travel time and costs. Based on the existing number of patients on Second Line ART and distance from CoE, it has been decided to expand the network of facilities providing ART, to ART Plus Centres that would be capacitated to start second line treatment following the same referral procedure as adopted for at the Centers of Excellence The ART Plus centres will be identified and linked to the nearby ART centres. The medical officers will be trained in Alternate First line ART and Second line ART in the nearest CoE.
Trainer Notes: The trainer informs the trainees on the sanctioned / functioning ART plus Centres in the country, as on March 2011. Discuss about the newly evolved ART Plus Centres. They are being created to help the patients to get Alternate first line ART and Second line ART initiated and remain on the treatment nearer to their place of living. This is a process of decentralisation in easy access to quality treatment aiming at reducing the travelling distance for PLHIV. Till November 2010, ART Plus centres have been initiated in the states of Maharashtra, Tamilnadu and Gujarat. The process will be expanded to cover all the states in the country very soon.
Step 6: Role of LAC in adherence (Slide 24) – 2 minutes Trainer Notes: The trainer can ask the participant, "What is the role of LAC in adherence?" The many different roles of an LAC are as follows: Functions of the Link ART Centre: A link ART centre needs to perform certain specific and important functions. The team at the Link ART centres has to be committed and should have a comprehensive understanding of these functions. Functions of ART centre can be categorised as medical, psychological and social as indicated below: 2.1. Medical Functions: To monitor the patients on ART in terms of OIs, Side Effects, Adherence and Weight. Back referral to the ART centre with reference to symptoms suggestive of OI, Side effect of drugs, Pregnancy and ANC care, etc. 2.2. Programmatic Functions : The LAC will be considered as important CST providing units under NACP III and they need to provide regular monthly reports and if necessary other relevant informations to Nodal ART Centre / SACS / NACO on demand. To facilitate linkages between other service providers such as ICTCs, NGOs and CBOs. 2.3. Psychological Functions To provide psychological support to PLHIV accessing the Link ART centre. To provide counselling for adherence to ARV drugs To educate PLHIV on proper nutrition. To advise for risk reduction behavior including usage of condoms. 2.4. Social Functions To facilitate PLHIV to access available resources provided by government and NGO agencies. To facilitate linkages between other service providers and patients, like educational help for the children and Income generation programmes.
Step 7: Role of CCC in adherence (Slide 25)- 2 minutes Trainer Notes: The trainer has to explain the important functions of a CCC. Adherence is one of the most important issues which need to be addressed by the CCC. The many different roles of an CCC are as follows: Counselling services Nutritional counselling and support Treatment and patient management – care for OI's and other illness. Referral and outreach Other support services.
Trainer Notes: The trainer has to provide the data on the number of PLHIV (adults and children) on ART. The data is updated up to December, 2010. .
Trainer Notes: The trainer has to provide the cumulative treatment outcome data of PLHIV, updated up to October, 2010.
Trainer Notes: Classify the different classes and the individual ARV drugs using the contents. Mention the ARVs (red colour) that are available in the National ART Programme.
Step 2: Monitoring and follow up of ARV Therapy (Slides 3-6) - 5 minutes Trainer Notes: Using the slide content, review the national first line regimens discussed in the previous session on "First line ART Initiation".
Trainer Notes: Discuss the adverse effects of ART depending upon the duration of ART.
Trainer Notes: Explain the alternate first line regimens III and IIIa and the situations where they are used.
Trainer Notes: Explain the alternate first line regimens IV and IV a and the situations where they are used.
Trainer Notes: Explain the eligibility criteria and time of initiation of ART in HIV-TB co infected patients using the table in the slide.
Trainer Notes: Explain the eligibility criteria and time of initiation of ART in Pregnant mothers using the table in the slide. Stress the need for monitoring Nevirapine toxicity in individuals, having CD4 count >250 cells.
Trainer Notes: Adequate and appropriate ARV prophylaxis, safe methods of delivery and good care of the mother during the antenatal period will help to decrease risk of transmission. This is a review of ARV interventions that summarise efforts to decrease the risk to babies. Our goal is to prevent the HIV transmission. ARV's require ongoing care and monitoring and reduce risk of PTCT in the following ways: Reduces viral replication and viral load. Treats maternal infection. Protects the HIV-exposed infant. Improves overall health of mother. Advantages of ART during pregnancy: Antiretroviral therapy reduces risk of transmission even in mothers with low baseline viral loads. Combination therapy with 3 drugs-ART can reduce transmission risk to <2% in many cases. Combination ART is the best way to prevent PTCT. Remember that in developed countries vertical transmission rarely happens, especially for women on ART (less than 70 nationwide in the U.S., 2003). ARV's are safe, well tolerated and easy to use in a pregnant woman who is carefully monitored. It is economical because it eliminates the need for the HIV care and treatment of infected babies (there will not be any, or they will be a few in number). Reduces the risk of the mother developing resistance, thereby preserving her future treatment options. GOI guidelines for PPTCT include single dose of Nevirapine for all pregnant positive women. Risks to infant (teratogenicity, preterm labour) appear to be minimal for most regimens. EFV has a teratogenic effect and is contraindicated in pregnancy. It should be avoided in women of child-bearing age who are not on effective contraceptives.
Step 2: Early infant diagnosis algorithm discussion (Slides 5-12) -15 minutes. Trainer notes: Trainer has to summarise the entire testing strategies using the flow diagram in the slide. Discuss the following questions about testing at 18 Months and Discordant results in testing. All three rapid tests are to be used at 18 months irrespective of the first test result, i.e. even if the first screening rapid test is negative, then proceed for the test 2 and 3. Ask the following question to the participants. Question 1: What do you do when you observe a discordant result during testing? Answer: In case discordance is observed between the test results obtained from the two specimens (DBS and whole blood) by the testing laboratory, a fresh whole blood specimen will be requested by the testing lab from the respective ART centre (test requisition cum result form) TRRF. The baby may be recalled for collection of fresh whole blood specimen for retesting on an urgent basis. The repeat specimen must be accompanied by a fresh TRRF that must specify that the specimen is a repeat specimen in the space provided and the reason why the repeat specimen was needed.
Trainer Notes: Trainer has to highlight the NEW recommendations for infants and children, as mentioned in the slide. Please remind the trainees these guidelines were discussed earlier in the session, "Management of HIV Exposed Infants and Children". Reiterate Presumptive diagnosis of severe HIV disease: 2 or more of following: Oral thrush Severe pneumonia Severe sepsis Initiate ART: Presumptive diagnosis of severe HIV disease in infants and children while awaiting the HIV test result. HIV antibody positive infants and children less than 18 months of age where virological testing is not available to confirm HIV infection should be considered for ART if they have Presumed Severe HIV disease All HIV- infected infants < 12 months of age, irrespective of clinical status and CD4 %/count
Trainer Notes: Trainer has to discuss the contents of the slide and to explain, why there is a need to revise the current guidelines ARV drugs decrease the viral load and thus decrease the transmission rates. Single dose NVP 200mg given at the onset of labour and single dose of syrup NVP 2mg/kg weight to the baby within 72 hours decreases risk of transmission by 13.1% (breast feeding). Advantages: Affordable, single dose easy administration, appropriate for resource poor settings. Disadvantages: Resistance even with single dose of NVP, which makes it difficult to treat mother if she needs ART for her own health in the near future. Baby may get infected with NVP resistant strains. If the women delivers within 2 hours of administering NVP, the baby needs syrup NVP 2mg/kg soon after delivery and a second dose at 72 hours of age. If a women gets NVP and the labour turns out be false labour, there is need to repeat NVP only if does not deliver in the next seven days. Studies have proved beyond doubt that AZT is most effective pre exposure prophylaxis for the baby. The drug is metabolised into its active form in the placenta and the mother to child drug concentration is also high. The first study PACTG 076 demonstrated starting AZT from 14 weeks, and the Thai studies started at 28 weeks and 36 weeks, which have proved very effective in preventing transmission in women that choose to breast feed as well as non breast feeding women. Transmission rates 8.3 %, 6.5%, 8.6 % (non breastfeeding). Reader Notes: ARV drugs decrease the viral load and thus decrease the transmission rates. Single dose NVP 200mg given at the onset of labour and single dose of syrup NVP 2mg/kg weight to the baby within 72 hours decreases risk of transmission by 13.1% (breast feeding). Advantages: Affordable, single dose easy administration, appropriate for resource poor settings. Disadvantages: Resistance even with single dose of NVP, which makes it difficult to treat mother if she needs ART for her own health in the near future. Baby may get infected with NVP resistant strains. If the women delivers within 2 hours of administering NVP, the baby needs syrup NVP 2mg/kg soon after delivery and a second dose at 72 hours of age. If a women gets NVP and the labour turns out be false labour, there is need to repeat NVP only if does not deliver in the next seven days.
Trainer Notes: Describe about HIV-2 using the slide contents
Step 6: Opportunistic Infections in Patients on ART ( Slides 46-49) - 15 minutes Trainer Notes: Discuss about OIs in a patient on ART with the participants, using the slide contents. Emphasise the need for T-staging the patient on ART on every monthly visit for monitoring purpose.
Trainer Notes: Discuss the need for follow up and the different components that are monitored during the follow up using the slide contents. The Trainer needs to mention that the viral load test will be done as per the decision made at SACEP/DACEP Meeting, to confirm the treatment failure. The trainer also needs to inform the participants that there will be separate session on SACEP/DACEP during the later part of the training.
Step 7: Tests for Monitoring (Slides 40-44) – 15 minutes Trainer Notes: Mention the objectives of HIV disease monitoring. Explain the direct marker –Viral Load Assay and Indirect marker – CD4 assay. Explain the definition of Viral load – Number of RNA copies per milliliter of blood or plasma Reader Notes: Tests are required to monitor to know about the disease progression, staging of disease and response to ART Tests available to monitor HIV are CD4 T-cell Assay and Viral load assay
Trainer Notes: The trainer may inform the participants about the CD4 counting methods. FACS Calibur/ FACS count/ Partec cyflow / Guava/EPICS XL(automated machines) Calculating percentage of CD4 cells using the formula when only the CD4 absolute count is available. Reader Notes: CD4 is the best measurement for assessing immune deficiency. CD4 should be used in conjunction with clinical assessment; however, CD4 allows an earlier detection of worsening of HIV disease as CD4 decline usually occurs prior to clinical progression. CD4 monitoring can aid in the decision to initiate or switch ART. Younger children normally have higher CD4 than older children and adults. %CD4 cells vary less in children < 6 years old and are the preferred measurement. Reference: Table-9, Page 16; Reference: Guidelines for HIV care and treatment in Infants and Children, November 2006,developed by Indian Academy of Paediatrics and National AIDS Control Organisation with support from Clinton Foundation, UNICEF and WHO)
Trainer Notes: All ART sites have access to CD4 testing. This may be done either within the campus, or the samples may need to be transported to a nearby location for testing. The choice for patients for CD4 testing is crucial to ensure that the kits are properly utilised. Reader Notes: All ART sites have access to CD4 testing. This may be done either within the campus, or the samples may need to be transported to a nearby location for testing. The choice for patients for CD4 testing is crucial to ensure that the kits are properly utilised.
Step 2: Definition, Synonyms & Diagnosis of IRIS (Slides 3-6; 8 minutes) Trainer Notes: Various set of criteria are proposed by different authors to define IRIS. Four of such criteria including one by NACO guidelines are included in this presentation. Pose the following question to the participants: What is IRIS? Select participants at random to answer the question. Refer participants to Handout 1 in the participant guide for synonyms used for IRIS in the literature. Reader Notes: Refer to Handout 1
Trainer Notes: Reiterate the points on the slide. Discuss the limitations in the definition – the late IRIS may not be picked up if this diagnosis is used fully Request the participants to come out with a definition now. Review the content on slides 4, 5 and 6 and then discuss the final definition.
Trainer Notes: Discuss the diagnostic criteria for IRIS. As viral load estimation is not available in programme for ART monitoring, give importance to CD4 in discussion.
Trainer Notes: Discuss the features of IRIS using the slide contents and also mention that there will be a separate session on IRIS in the training programme. The trainer may mention the following point; though the NACO definition mentions occurrence of IRIS up to 6 months after the start of ART, the IRIS can occur even after 6 months (late IRIS- Literature mentions even after 3 years after ART initiation, IRIS can occur)
Step 4: Clinical Profile & Literature Evidence: Aetiology, Patterns & Clinical spectrum of IRIS (Slides 10-17; 16 minutes) Trainer Notes: Discuss some of the infectious clinical conditions observed as IRIS
Trainer Notes: Discuss some of the non infectious conditions observed as IRIS after initiating ART
Trainer Notes: Explain the pathogenesis of IRIS in simple terms. Refer participants to Handout 2 in the participant guide. Reader Notes: Refer to Handout 2.
Step 6: Differential diagnosis, Management & Prevention of IRIS (Slides 28-32; 6 minutes) Trainer Notes: Discuss the differential diagnosis of IRIS
Trainer Notes: Explain the management of IRIS depending upon the severity of IRIS.
Trainer Notes: Review the points on the slide. Encourage discussion.
Step 1: Introduction & Session Objectives (Slides1-2; 1 minute) Trainer Notes: This session will take approximately 90 minutes to complete. Step 1: Introduction & Session Objectives (Slides1-2; 1 minute) Step 2: Treatment Failure: definition, identification and case studies (Slides 3-14; 10 minutes) Step 3: CoE and SACEP / ART Plus Centres and DACEP: Jurisdiction/linkages (slides 15-23); 20 minutes Step 4: Energisers ( Slide 24) – 3 minutes Step 5: SACEP / DACEP: Protocols, referral mechanism, Alternate First line ART (slides 25-30); 10 minutes Step 6: SACEP / DACEP: Protocols, referral mechanism, Second line ART (slides 31-44) 20 minutes Step 7: National Second line ART Regimen, formulation and Side Effects (Slides 45-52; 10 minutes) Step 8: Key Points (Slide 53; 1 minute)
Trainer Notes: Using the graph explain to the participants that during the course of ART, the virological failure occurs first, followed by the immunological failure, and finally the clinical failure occur. Highlight the point that viral load assessment is to be done regularly in order to detect the treatment failure at an early stage. In identifying treatment failure a HIGH INDEX of suspicion is required; Look for the following among patients who have been receiving first line ART for at least 6 months: A new OI or a clinical event after 6 months of first line ART, after ruling out IRIS. Clinical deterioration in spite of good adherence to therapy. Progressive CD4 decline. Slow/no clinical improvement over 6-12 months, associated with stationary CD4, despite good adherence.
Trainer Notes: Highlight the importance of High index of suspicion in Identifying Treatment Failure, using the slide contents
Trainer Notes: Review points to summarise the criteria for clinical, immunological and virological failure. Source: National Guidelines on Second-line ART for adults and adolescents, November 2008; page 16; Table 5: Clinical, immunological and virological definitions of treatment failure for first-line regimen.
Step 3: CoE and SACEP / ART Plus Centres and DACEP: Jurisdiction/linkages (slides 15-23); 20 minutes Trainer Notes: Describe the constitution of SACEP using the slide contents. Source: National Guidelines on Second-line ART for adults and adolescents, November 2008; page 55-58
Trainer Notes: Describe the constitution of DACEP using the slide contents.
Trainer Notes: Describe the meeting schedule of SACEP / DACEP using the slide contents. Source: National Guidelines on Second-line ART for adults and adolescents, November 2008; page 55-58
Trainer Notes: Describe the steps to be taken based on the viral load result. Source: National Guidelines on Second-line ART for adults and adolescents, November 2008; page 60.
Trainer Notes: Discuss the national Second-line ART regimens. Source: National Guidelines on Second-line ART for adults and adolescents, November 2008; page 23
Trainer Notes: The trainer has to provide the data on the number of PLHIV on Second line ART under National ART Programme in India. Second line ART was initiated in January 2008 first in two sites as a pilot and then expanded to all the Centres of Excellence.
Trainer Notes: Describe the eligibility criteria for the universal access to Second line ART and describe the procedures to be followed. Source: Amendment to National Guidelines on Second-line ART for adults and adolescents, December, 2010.
Trainer Notes: Give the details of the recommendations made by Technical Resource Group (TRG) of NACO in August 2010. Decision to implement this will be taken after estimating additional financial resources required, budgetary provisions and procurement related issues
Step 7: Issues and Challenges in care and support service (Slide 55) -2 minutes Trainer Notes: The trainer to list the challenges of the National ART programme He may request the participants to list the issues and challenges on the flip chart and then project the slide The trainer has to emphasise all these issues will be detailed in the relevant sessions
Transcript of "Talk on HIV infection"
… A long WALK with HIV…. .. a small Talk on ART !!
<ul><li>ART……. !!!.... Will it pave the way for success ..? </li></ul>
Progression to AIDS / Death Months % of patients progressing No therapy Mono-therapy Dual-therapy Triple therapy Source: NEJM
Some facts about ART <ul><li>1996 - PIs were introduced - era of HAART came in </li></ul><ul><li>Then - high costs, large number of pills and side effects of these drugs </li></ul><ul><li>Now cost of Therapy reduced from </li></ul><ul><li>Rs.30,000 in 1998 to Rs1000 per month in 2006, </li></ul><ul><li>no. of pills from 32 to 1 or 2 per day, </li></ul><ul><li>regimens simplified, fewer side effects with newer drugs </li></ul>
Antiretroviral Therapy (ART) <ul><li>ART is the combination of different classes of ARV drugs </li></ul><ul><ul><li>To achieve maximal and most durable suppression of viral replication </li></ul></ul><ul><ul><li>To prevent emergence of drug resistant mutants </li></ul></ul><ul><ul><li>To improve survival & quality of life </li></ul></ul>Images Courtesy GHTM Tambaram /I-TECH After ART
Do all Patients with HIV Infection Need ART? Patients with higher CD4 counts e.g. >500 cells/cumm do not have additional survival benefit from ART & The risk from ART toxicities is high (especially Nevirapine) in patients with higher CD4 counts - determine eligibility for ART - based on clinical and immunological criteria
Indications for Initiation of ART National Guidelines, April 2009 WHO Clinical Staging CD4 (cells/cu.mm) I and II Treat if CD4 Count <250 III Treat if CD4 Count <350 IV Treat irrespective of CD4 Count
WHO Clinical Staging I <ul><ul><li>Asymptomatic </li></ul></ul><ul><ul><li>Persistent generalised lymphadenopathy (PGL) </li></ul></ul><ul><ul><ul><li>Painless </li></ul></ul></ul><ul><ul><ul><li>non-contiguous sites (excluding inguinal) </li></ul></ul></ul><ul><ul><ul><li>bsence of known cause </li></ul></ul></ul><ul><ul><ul><li>Persisting for 3 months </li></ul></ul></ul>
WHO Clinical Staging 2 <ul><li>moderate weight loss (<10% of presumed or measured body weight) </li></ul><ul><li>Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media, pharyngitis) </li></ul><ul><li>Herpes zoster </li></ul><ul><li>Recurrent oral ulceration </li></ul><ul><li>Seborrhoeic dermatitis </li></ul><ul><li>Fungal nail infections </li></ul>
WHO Clinical Staging 3 <ul><li>severe weight loss (>10% of presumed or measured body weight) </li></ul><ul><li>chronic diarrhoea for longer than one month </li></ul><ul><li>persistent fever longer than one month </li></ul><ul><li>Persistent oral candidiasis </li></ul><ul><li>Oral hairy leukoplakia (OHL) </li></ul><ul><li>Pulmonary tuberculosis cont...... </li></ul>
……… ..WHO Clinical Staging 3 <ul><li>Severe bacterial infections </li></ul><ul><li>Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis </li></ul><ul><li>Unexplained </li></ul><ul><ul><li>Anaemia (<8 g/dl ) </li></ul></ul><ul><ul><li>Neutropenia (<0.5 x 10 9 /L) and or </li></ul></ul><ul><ul><li>Chronic thrombocytopenia (<50 X 10 9 /L) </li></ul></ul>
WHO Clinical Staging 4 <ul><li>HIV wasting syndrome </li></ul><ul><li>Pneumocystis pneumonia (PCP) </li></ul><ul><li>Recurrent severe bacterial pneumonia </li></ul><ul><li>Oesophageal candidiasis </li></ul><ul><li>Extra pulmonary tuberculosis </li></ul><ul><li>Kaposi's sarcoma </li></ul><ul><li>cont…….. </li></ul>
……… WHO Clinical Staging 4 <ul><li>Central nervous system toxoplasmosis </li></ul><ul><li>HIV encephalopathy </li></ul><ul><li>Extra pulmonary cryptococcosis </li></ul><ul><li>Disseminated non-tuberculous mycobacteria infection </li></ul><ul><li>Chronic cryptosporidiosis, isosporiasis </li></ul><ul><li>cont…… </li></ul>
……… .WHO Clinical Staging 4 <ul><li>Disseminated mycosis (extra pulmonary histoplasmosis, coccidiomycosis) </li></ul><ul><li>Lymphoma (cerebral or B cell non-Hodgkin) </li></ul><ul><li>Invasive cervical carcinoma </li></ul><ul><li>Atypical disseminated leishmaniasis </li></ul><ul><li>HIV associated nephropathy or cardiomyopathy </li></ul>
NACO ART services Three Tier model <ul><li>Care & Support : Community Care Centre (CCC) </li></ul>
<ul><li>good quality, skilled and knowledgeable healthcare providers </li></ul><ul><li>in chronic patient management, including treatment failures </li></ul><ul><li>Training HIV Care personnel </li></ul><ul><li>Operational Research and scientific publications </li></ul><ul><li>Fellowship Programmes for doctors </li></ul><ul><li>Mentoring ART centres in the region / state </li></ul>Centre of Excellence
<ul><li>Chandigarh </li></ul><ul><li>New Delhi </li></ul><ul><li>Varanasi </li></ul><ul><li>Imphal </li></ul><ul><li>Kolkata </li></ul><ul><li>Ahmadabad </li></ul><ul><li>Mumbai </li></ul><ul><li>Hyderabad </li></ul><ul><li>Bengaluru </li></ul><ul><li>Chennai </li></ul>COE Centres of Excellence
Centres of Excellence & ART Centres for Referrals No COE ART Centres 1 Government Hospital of Thoracic Medicine (GHTM), Tambaram , Chennai Allotted ART centres in Tamil Nadu, Kerala, Pondicherry & ART centres of Tirupathi, Nellore & Chittoor 2 Sir J.J. Hospital, Mumbai Allotted ART centres in Maharashtra, Madhya Pradesh & Goa 3 Government Gandhi General Hospital , Hyderabad All ART centres in Andhra Pradesh (except ART centres of Tirupathi, Nellore & Chittoor) 4 Bowring and Lady Curzon Hospital, Bangalore All ART centres in Karnataka 5 Bairamji Jijibhai Medical College (BJMC), Ahmedabad Allotted ART centres in Gujarat & ART centres of Udaipur & Jodhpur
Centres of Excellence & ART Centres for Referrals No COE ART Centres 6 Maulana Azad Medical College (MAMC), New Delhi All ART centres in New Delhi, Rajasthan (except Udaipur & Jodhpur), Uttarakhand & ART centres in Meerut, Aligarh & Agra 7 Post Graduate Institute of Medical Education & Research (PGIMER) , Chandigarh All ART centres in Himachal Pradesh, Haryana, Punjab, Chandigarh, Jammu & Kashmir 8 School of Tropical Medicine, Kolkata All ART centres in West Bengal, Orissa, Jharkhand, Chhattisgarh, Assam and Sikkim 9 BHU Varanasi All ART centres in UP (except Meerut, Agra & Aligarh) & Bihar 10 RIMS , Imphal All ART centres in North Eastern States
ART Plus Centres: Rationale <ul><li>To combat Problems - treatment failure with First Line ART are referred to the CoE for further evaluation and Second Line treatment. </li></ul><ul><li>facing problems due to long distance, travel, time and costs. </li></ul><ul><li>it has been decided to expand the network of ART centres that would be capacitated to start Second Line treatment </li></ul>
<ul><li>Govt. Medical College, Salem (Functioning) </li></ul><ul><li>Govt. Medical College, Aurangabad (Oriented) </li></ul><ul><li>Byramjee Jejeebhoy Medical College & Sasoon Hospital, Pune (Oriented) </li></ul><ul><li>Govt. Medical College, Nagpur (Oriented) </li></ul><ul><li>Govt. Medical College, Surat (Oriented) </li></ul><ul><li>KIMS, Hubli, Karnataka (Sanctioned) </li></ul><ul><li>GGH, Vijayawada, Andhra Pradesh (Sanctioned) </li></ul><ul><li>Govt. Medical College, Trichur, Kerala (Sanctioned) </li></ul>ART Plus Centres As on March 2011
Role of Link ART Centres <ul><li>LAC reduces travel from long distances to access ART Services </li></ul><ul><li>Designed to enhance ART Adherence </li></ul>LAC Back Referral to ART Centre Screening of HIV-TB Co infection Psycho-Social Support To PLHIV Treatment of Minor OIs Provide ARV Drugs to Stable PLHIV on ART Adherence Counselling and Monitoring PLHIV for side effects
Role of CCC in ART <ul><li>Drug Adherence and nutritional counselling </li></ul><ul><li>tracing missed cases and those lost to follow-up through outreach workers </li></ul><ul><li>Psycho-social support </li></ul><ul><li>Home-based care for bedridden patients </li></ul>
ART programme: Current Scenario Updated December 2010 Total number of patients on ART : 3,84,726 <ul><li>% Adults </li></ul><ul><li>% Children </li></ul>: 94 % : 6% No. of new adult patients on ART per month No. of new children patients on ART per month : 7000 : 350
Treatment Outcome: Cumulative Updated October 2010
Classes of ARV Drugs NRTI NNRTI Protease Inhibitor OTHERS Zidovudine (AZT)* Nevirapine (NVP)* Lopinavir (LPV)* Integrase Inhibitors Stavudine (d4T)* Efavirenz (EFV)* Ritonavir (RTV)* Raltegravir Lamivudine (3TC)* Atazanavir (ATV) Fusion Inhibitor Emtricitabine (FTC) Saquinavir (SQV) Enfuviritide (T-20) Didanosine (ddI ) Indinavir (IDV) Chemokine Co Receptor (CCR5 / CXCR4) Antagonists) Abacavir (ABC) Nelfinavir (NFV) NtRTI Amprenavir (APV) Tenofovir (TDF)* Fosamprenavir, (FPV), Tipranavir (TPV), Darunavir (DRV) Maraviroc (CCR5 co receptor antagonists) * The highlighted drugs are NOW available in the NACO ART programme
National First line ART Recommended First Line Drugs : 2NRTI +1 NNRTI National ART Regimen Drugs Regimen I Zidovudine + Lamivudine + Nevirapine Regimen I (a) Stavudine + Lamivudine + Nevirapine Regimen II Zidovudine + Lamivudine + Efavirenz Regimen II (a) Stavudine + Lamivudine + Efavirenz
First line ART: Drug Toxicities Drugs Short term toxicities Medium term toxicities Long term toxicities Zidovudine Nausea, vomiting, Diarrhoea Bone Marrow suppression Anaemia Hyper pigmentation Lactic Acidosis Lipodystrophy Stavudine Lactic Acidosis Pancreatitis Peripheral Neuritis Lipodystrophy Dyslipidemia Lamivudine Skin Rashes Nevirapine Skin Rashes Hepato toxicity Efavirenz Skin Rashes Hepato toxicity Drowsiness, dizziness Confusion, Vivid dreams
Alternate to Zidovudine & Stavudine Alternate First line ART Regimen Drug Combination Remarks Regimen III Tenofovir + Lamivudine + Nevirapine For patients not tolerating Zidovudine and Stavudine Regimen III (a) Tenofovir + Lamivudine + Efavirenz
Alternate to Nevirapine & Efavirenz In patients with confirmed HIV 2 infection Alternate First line ART Regimen Drug Combination Remarks Regimen IV Zidovudine + Lamivudine + Lopinavir / Ritonavir For patients not tolerating both NVP & EFV Regimen IV (a) Stavudine + Lamivudine + Lopinavir / Ritonavir For patients not tolerating both NVP & EFV and Hb <9 g%
<ul><li>ART in special situations……. </li></ul>
ART in HIV and TB Type of TB CD4 cell count (cells/ mm 3 ) Timing of ART in relation to start of TB treatment ART Recommendations Pulmonary TB CD4 <350 Start ATT first Start ART as soon as TB treatment is tolerated (after 2 weeks & before 2 months) Recommend ART. EFV containing Regimens Extra pulmonary TB irrespective of CD4 count Start ATT first Start ART as soon as TB treatment is tolerated (after 2 weeks & before 2 months) Recommend ART. EFV containing regimens Special Attention to be paid for monitoring Hepato toxicity
ART in Pregnancy Guidelines for initiation of ART (2010) WHO Clinical Staging CD4 (cells/cu.mm) I and II Start ART at CD4 Count <350 III & IV Start ART irrespective of CD4 Count Avoid Efavirenz during First Trimester of Pregnancy Strict Monitoring for Adverse effects of Nevirapine is needed if CD4 count is >250
ARV / PTCT Source: WHO Intervention Risk of Mother-to-Child HIV Transmission No ARV, breastfeeding 30-45% No ARV, No breastfeeding 20-25% Short course with 1 ARV, breastfeeding 15-25% Short course with 1 ARV, No breastfeeding 5-15% Short course with 2 ARVs, no breastfeeding 5% 3 ARVs (ART), no breastfeeding 1%
Care of HIV Exposed Infants & Children Rapid antibody test not recommended 6 weeks 10 weeks 14 weeks 6 months 9 months 12 months 18 months DNA PCR for all HIV exposed infants DNA PCR HIV Antibody test followed by DNA PCR if HIV+ Final confirmatory Antibody Test for all HIV exposed infants irrespective of earlier testing results / treatment status Birth Schedule of visits at ICTC
ART in Infants (<12 Months) <ul><li>Criteria for starting ART </li></ul><ul><li>- All infants under 12 months of age with confirmed HIV infection irrespective of clinical or immunological stage </li></ul><ul><li>- Where virological testing is not available, infants under 12 months of age with clinically diagnosed presumptive severe HIV should start antiretroviral therapy </li></ul>
Monotherapy as Prophylaxis <ul><li>Nevirapine (NACO Guidelines) </li></ul><ul><ul><li>Mother - Single dose NVP 200mg onset of labour </li></ul></ul><ul><ul><li>Baby - Syrup NVP 2mg/kg within 72 hours of delivery </li></ul></ul><ul><li>Revised NACO Guidelines will be in place shortly </li></ul>
ART & HIV-2 <ul><li>Primarily seen in West Africa </li></ul><ul><li>Less transmissibility as compared to HIV-1 </li></ul><ul><li>Slower rate of progression </li></ul><ul><li>Low MTCT </li></ul><ul><li>No viral load assay available </li></ul><ul><li>NNRTI are ineffective </li></ul><ul><li>PI-based ART (AZT/d4T + 3TC + LPV/r) </li></ul>
OI ….??..... ART <ul><ul><li>OIs shortly after initiating ART (within 12 weeks) - </li></ul></ul><ul><ul><li>There is no change or mild increase in CD4 counts - either sub clinical infections or due to advanced disease </li></ul></ul><ul><ul><li>OI after 12 weeks after initiation of therapy </li></ul></ul><ul><ul><ul><li>There is a marked raise in CD4 counts - IRIS </li></ul></ul></ul><ul><ul><li>OI as the manifestation of failing ART regimen </li></ul></ul><ul><ul><li>Patients have a failing CD4 count – treatment failure </li></ul></ul>
<ul><li>Clinical monitoring – Monthly </li></ul><ul><ul><li>Clinical Evaluation </li></ul></ul><ul><ul><li>Treatment Adherence Evaluation </li></ul></ul><ul><ul><li>For Adverse reactions of ART/OI drugs </li></ul></ul><ul><ul><li>For drug interactions </li></ul></ul><ul><ul><li>For Immune Reconstitution Inflammatory Syndrome </li></ul></ul><ul><li>Immunological monitoring </li></ul><ul><ul><li>CD4 count </li></ul></ul><ul><li>Virological test (Targeted Viral load test) - PCR </li></ul><ul><ul><li>(SACEP/DACEP) </li></ul></ul>Follow up of ART
<ul><li>Tests are required to monitor </li></ul><ul><li>- Disease progression </li></ul><ul><li>- Staging of disease </li></ul><ul><li>- Response to ART </li></ul><ul><li>Include - CD4 T-cell Assay </li></ul><ul><li> - Viral load assay </li></ul>Tests for Monitoring HIV/ART
CD4 counts and CD4 % <ul><li>assess immunological status of the HIV-infected </li></ul><ul><li>Varies due to diurnal change, undercurrent illness, steroid treatment, splenectomy, after immunisations </li></ul><ul><li>repeated measurements are more informative than single value </li></ul><ul><li>CD4 counts are higher in infants as compared to adults and fall to adult values by age 5 </li></ul><ul><li>CD4% varies less than CD4 counts, hence considered more valuable in children <5 years of age </li></ul>
When to Perform CD4 Test <ul><li>All HIV patients accessing Hospitals - immediately after their HIV status known </li></ul><ul><li>Pre-ART: once in 6 months till they are being initiated on ART </li></ul><ul><li>During ART: </li></ul><ul><ul><li>Once in 6 months for monitoring </li></ul></ul><ul><ul><li>As and when their clinical conditions demand </li></ul></ul>
IRIS - Definition <ul><li>The worsening of signs and symptoms due to known infections or the development of disease due to occult infections, that results from an inflammatory response by a re-invigorated immune system following the initiation of anti-retroviral therapy </li></ul>
Practical Definition: NACO <ul><li>" Occurrence or manifestations of new Opportunistic Infections within six weeks to six months after initiating ART - with increase in CD4 count" </li></ul>Source: National AIDS Control Organisation, India (NACO): Antiretroviral Therapy Guidelines for HIV-infected Adults and Adolescents Including Post-exposure Prophylaxis. May 2007
Criteria for Diagnosing IRIS <ul><li>HIV positive </li></ul><ul><li>Receiving ART </li></ul><ul><ul><li>Decrease in HIV-1 RNA level from baseline </li></ul></ul><ul><ul><li>Increase in CD4 cells from baseline </li></ul></ul><ul><li>Clinical symptoms consistent with inflammatory process </li></ul><ul><li>Clinical course NOT consistent with OI </li></ul><ul><ul><li>Source: Samuel A. Shelburne, Martin Montes and Richard J. Hamill Journal of Antimicrobial Chemotherapy, Source: (2006) 57, 167-170. </li></ul></ul>
Immune Reconstitution Inflammatory Syndrome (IRIS) <ul><li>Can happen with any ART initiation, especially in PLHIV presenting with very low CD4 count </li></ul><ul><li>" manifestations of new OIs within six weeks to six months after initiating ART; with increase in CD4 count" </li></ul><ul><li>Common conditions associated with: </li></ul><ul><li>Tuberculosis - 68.8% , Herpes zoster - 12.5% , Cryptococcal Meningitis - 9.4%, Toxoplasmosis- 6.3%, Bacterial Pneumonia- 3.1% </li></ul>
Infectious Causes of IRIS <ul><li>Mycobacteria </li></ul><ul><ul><li>Mycobacterium tuberculosis </li></ul></ul><ul><ul><li>MAIC </li></ul></ul><ul><li>Cytomegalovirus </li></ul><ul><li>Herpes viruses </li></ul><ul><li>Cryptococcus neoformans </li></ul><ul><li>Pneumocystis jirovecii pneumonia </li></ul><ul><li>Histoplasmosis capsulatum </li></ul><ul><li>Toxoplasmosis </li></ul><ul><li>Hepatitis B Virus </li></ul><ul><li>Hepatitis C Virus </li></ul><ul><li>Progressive multifocal leukoencephalopathy </li></ul><ul><li>Parvovirus B 19 </li></ul><ul><li>Molluscum contagiosum & genital warts </li></ul><ul><li>Sinusistis </li></ul><ul><li>Folliculitis </li></ul><ul><li>Strongyloides stercoralis & other parasitic infections </li></ul>
Non-Infectious Causes of IRIS <ul><li>Autoimmune IRIS </li></ul><ul><li>Rheumatoid arthritis </li></ul><ul><li>SLE </li></ul><ul><li>Graves disease </li></ul><ul><li>Autoimmune thyroid disease </li></ul><ul><li>Sarcoid IRIS </li></ul><ul><li>Granulomatous reactions </li></ul><ul><li>Other Rare Manifestations </li></ul><ul><li>AIDS-related lymphoma </li></ul><ul><li>Guillain-Barre' syndrome </li></ul><ul><li>Interstitial lymphoid pneumonitis </li></ul>
Pathogenesis of IRIS <ul><li>Improved Cell Mediated Immunity with restoration of both memory and naïve CD4 cells </li></ul><ul><li>Increased CD4/CD8 cells detect hidden pathogens which were ignored with deficiency of immunity previously </li></ul><ul><li>Result in inflammatory process at the area of occult / sub-clinical infections </li></ul><ul><li>Usually improves with control of inflammation and specific treatment </li></ul>
IRIS: Differential Diagnosis <ul><li>Failure of ART </li></ul><ul><li>ART Toxicity </li></ul><ul><li>Active Opportunistic Infections </li></ul><ul><li>Failure of Antimicrobial Therapy </li></ul>
Management <ul><li>Mild form (with ongoing ART) </li></ul><ul><ul><li>Observation </li></ul></ul><ul><li>Localised IRIS (with ongoing ART) </li></ul><ul><ul><li>Local therapy such as minor surgical procedures for lymph node abscesses </li></ul></ul><ul><ul><li>Severe IRIS - Temporary cessation of ART has to be considered </li></ul></ul>
Prevention of IRIS <ul><li>Keeping high vigilance in patients who are at risk of developing IRIS during the introduction phase of ART </li></ul><ul><li>Measures taken to reduce pathogen load </li></ul><ul><li>Delay initiation of ART few weeks until pathogen load is decreased by using appropriate anti- microbial agents </li></ul>
Second line ART and SACEP / DACEP
<ul><li>Second line regimen </li></ul><ul><li>is "the next regimen used in sequence immediately after first-line therapy has failed" </li></ul><ul><li>Treatment Failure </li></ul><ul><li>refers to the loss of antiviral efficacy </li></ul><ul><li>identified by clinical, immunological and/or virological monitoring. </li></ul>
Treatment Failure: Time of detection Treatment Failure Virologic detection Immunologic detection Time Viral Load Clinical Status CD4 Count Clinical detection
<ul><li>High index of suspicion is the key </li></ul><ul><li>patients on first line ART for at least 6 months: </li></ul><ul><ul><li>New OIs/recurrence/clinical events after 6 months on first line ART (after ruling out IRIS) </li></ul></ul><ul><ul><li>Clinical deterioration in spite of good adherence to therapy </li></ul></ul><ul><ul><li>Progressive CD4 count decline </li></ul></ul><ul><ul><li>Viral load testing to confirm treatment failure </li></ul></ul><ul><ul><li>Review by the SACEP / DACEP </li></ul></ul>Identifying Treatment Failure
Defining Treatment Failure Source: National Second line ART guidelines, Nov 2008 Clinical failure New or recurrent WHO stage 4 condition, after at least 6 months of 1 st line ART Immunological failure <ul><li>Fall of CD4 count to pre-therapy </li></ul><ul><li>50% fall from the on-treatment peak value </li></ul><ul><li>Persistent CD4 levels below 100 cells/mm </li></ul>Virological Failure Plasma viral load >5,000 copies/ml after at least 6 months of 1 st line ART
State AIDS Clinical Expert Panel (SACEP) <ul><li>The SACEP consists of </li></ul><ul><ul><li>Nodal Officer of Centre of Excellence </li></ul></ul><ul><ul><li>One more ART expert (from the names provided by NACO) </li></ul></ul><ul><ul><li>Joint Director (CST) / Regional Coordinator / Consultant (CST) at SACS where SACEP is located </li></ul></ul><ul><ul><li>Paediatrician from CoE if there are paediatric patients on that particular day </li></ul></ul><ul><li>observers from central level for monitoring purposes </li></ul>
District AIDS Clinical Expert Panel (DACEP) <ul><li>The DACEP consists of </li></ul><ul><ul><li>Nodal Officer of ART Plus Centre </li></ul></ul><ul><ul><li>One more ART expert (from the names provided by NACO) </li></ul></ul><ul><ul><li>Designated representative from SACS/DPM/DAPCU / Regional Coordinator </li></ul></ul><ul><ul><li>Paediatrician from ART Plus Centre shall be present if there are paediatric patients on that particular day </li></ul></ul><ul><li>observers from central / state level for monitoring purposes </li></ul>
<ul><li>SACEP / DACEP meets at the Centre of Excellence (CoE) or ART Plus Centre to review cases weekly or fortnightly on a designated week day (for e.g. Tuesday) </li></ul><ul><li>It meets next working day in case designated week day happens to be a holiday (for e.g. Wednesday) </li></ul><ul><li>A maximum of 20 new patients shall be reviewed at each meeting </li></ul>SACEP / DACEP meetings
05/04/11 Confirming Virological Failure CD4 & Viral load Monitoring once in 6 months Repeat CD4 & viral load In 3 months Initiate Second line ART
<ul><li>Preferred Second line regimen: </li></ul><ul><ul><li>Lopinavir / Ritonavir + Tenofovir + Lamivudine + </li></ul></ul><ul><ul><li>Zidovudine (Patients with Hb > 9 g/dl) </li></ul></ul><ul><li>Alternate Second line regimen: </li></ul><ul><ul><li>Lopinavir / Ritonavir + Tenofovir + Lamivudine </li></ul></ul><ul><ul><li>(Patients with Hb <9 g/dl) </li></ul></ul>Second line ART Regimens
PLHIV on Second line ART Updated December 2010
<ul><li>second line ART now available to all those in need of it because of treatment failure - whether they underwent first line treatment in the government sector or private sector, in a phased manner. </li></ul><ul><li>In the first phase - started at four Centres of Excellence (JJ Hospital in Mumbai, GHTM Tambaram, MAMC, New Delhi and STM, Kolkata) with immediate effect. This will be open to patients from any part of the country. </li></ul>Universal access to second line ART
New Recommendations <ul><ul><li>- increase the CD4 cut off point to 350 cells/mm 3 in India </li></ul></ul><ul><ul><li>- initiate ART in all HIV-TB co-infected patients, irrespective of CD4 count. </li></ul></ul>
Issues and Challenges <ul><li>Low referrals from ICTC to ART centres </li></ul><ul><li>Pre-ART care and Follow up </li></ul><ul><li>Ensuring optimal (> 95%) adherence to ART </li></ul><ul><li>Timely and Early initiation of ART </li></ul><ul><li>Tracking patients Lost to follow up (LFU) </li></ul><ul><li>Second line ART </li></ul><ul><li>Linkages with RNTCP and other local networks </li></ul><ul><li>Irrational ART Prescriptions outside National Programme </li></ul>
HIV…ART…WE… <ul><li>walk together for success </li></ul><ul><li>but </li></ul><ul><li>mind the gaps </li></ul>
<ul><li>Created by Dr. K.Prasanthi MD for e learning resources for Medical Professionals in the Developing World </li></ul><ul><li>Email </li></ul><ul><li>[email_address] </li></ul>


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Author City: BROOKLYN, NY USAJohn High ranks among the most accomplished and respected poets, translators, and editors of his generation. Founding editor of Five Fingers Review and author of THE LIVES OF THOMAS, The Sasha Poems, THE DESIRE NOTEBOOKS, BLOODLINE: SELECTED WRITINGS, HERE, and A BOOK OF UNKNOWNING, among others, he is one of his generation's foremost translators of contemporary Russian poetry. The principal editor of CROSSING CENTURIES: THE NEW GENERATION IN RUSSIAN POETRY, he is known for his translations of Nina Iskrenko, Ivan Zhdanov, and Alexei Parschikov, among others. A former Fulbright professor at Moscow State Linguistics University, he currently teaches at Long Island University.
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...g her again. "Don't worry, Tonks," she said, smiling widely, "I'm pretty sure I know." Tonks blushed even brighter, mumbling something intelligible. They sat there for a while, making small talk as they waited. Madame Pomfrey had been in the room with Harry and Bellatrix for the past few hours, and anyone who tried to enter eventually ran out, screaming bloody murder, the victim of a nasty itching hex. Madame Pomfrey, it seemed, was not one to be trifled with when working with a patient. The door to the bedroom opened with a squeak, and Tonks immediately leapt to her feet, rushing over to Madam Pomfrey. "Is he alright?" she asked, a worried expression on her face, "Can I see him?" Pomfrey sighed. "Sit down, Tonks, I have something very serious to talk to you about. Actually, you can see him now. I've given him a sleeping potion, so he'll be unconscious for the next eight hours or so. In a few minutes, I'll need you downstairs. I need to talk to the Order about something very serious." Tonks began crying again, and Fleur held her sobbing form tightly, comfortingly running her hand up and down her back. "What happened?" Tonks asked, a desperate note in her tone, "What did they do to him?" Pomfrey sighed. "It isn't irreversible, Tonks, so try to calm dow...
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The Kinetis KL0 MCU family is the entry point into the Kinetis L series based on the ARM® Cortex®-M0+ core. The KL0 ultra-low-power MCUs provide a bridge for 8-bit customers migrating into the Kinetis portfolio and is software and tool compatible with all other Kinetis L series devices.
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Soaking up the Caribbean? You'd better Belize it!
... as he then offered us some local pharmaceuticals in whispered tones before skulking off, dissappointed. We were very happy to be staying on the neighbouring island, where the population were more genuinely friendly and less tarnished by the tourist trade. Our second dive at Esmerelda Canyons was spectacular. It started off close to a spot where a whole school of nurse sharks were circling close to a rock inhabited by a green moray eel. The canyons were formed from small ...
"Cos it's hotta anda da watta"
... the meal we invited Dustin, Leo and Piero to join us for the dinner and we enjoyed a delicious chicken curry with rice and baked plantanes (bananas).
On the sunny days we mainly looked for refreshing. Either we went swimming at the split - the little channel that connects Caye Caulker with the little island next to it - and on the really warm and humid days we just had to walk on the other side of the island to find the onshore winds that cooled ...
I Don't Belize It
I checked into my new hostel in the morning, before going off to explore. The island is small, and you can walk the length of the main strip in maybe fifteen minutes. There is one primary road north to south, that follow the eastern shore. Other roads break off at right angles. Further towards the south where the island widdens a few more roads run in parallel. They are all made of ...
Day 37
... get tired. If you have ever seen a cow being airlifted in one of those harnesses that's exactly what he looked like. You'd have been in tears if you'd seen this. Me and Sheeno were in stitches. We saw so many fish at Hol Chan. These aren't the type of fish you can buy it Petworld in Carrickmines these ones have incredible colours and designs on them. The Barracudas were enormous as well and would have no hesitation in swimming right up to you and then move away at ...
Belize at last.
... a gyro wrap which was a new food for me. It turned out to be one of the best meals on this trip so far. After dinner we went back to our hotel room. Sadly, it was only one room with two double beds. So I had to put up with Ed's snoring once again. The industrial strength earplugs plus wrapping a pillow around my head helped ...


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(HOLLYWOOD, CA) -- Viva Las Vegas! Ultra-sexy starlet Angelina Armani (http://www.myspace.com/angelinaarmani) is setting her sights on the XBIZ Summer Forum (http://www.xbizsummerforum.com/) in the City of Sin! Its a sure bet that the 2009 Xsc is going to be the hottest thing in Vegas this week as the reigning ''it-Girl'' of adult entertainment will be rocking the show with her enticing presence. Armani continues to make a name for herself as a fast rising starlet whose performances are a big hit with fans and critics alike. Recently Angelina wowed her fans with her appearance at the packed Exxxotica Miami Beach event then hit the west coast with stop by the Webmaster Access show in Universal City. An always on the move beauty, Armani is now headed to Las Vegas.
''I have wanted to go to the XBIZ Summer Forum since I first heard about it,'' said Armani. ''Its going to be a fun sexy time. There are a lot of interesting events happening and most of it by the Hard Rock Hotels pool, which is where youll find me. In high heels and a bikini of course!''
The XBIZ Summer Forum takes place at the Hard Rock Hotel beginning this Wednesday, June 3rd and continues through Friday. The shows website describes the annual event as bringing ''together the industry's top decision-makers from around the globe for three days of high-energy networking, deal-making and online business workshops.'' More information can be found on the events site: xbizsummerforum.com.
Everyone is invited to follow Armanis adventures as the golden haired beauty will be twittering her Vegas stay. Already an avid user of the popular micro- blogging site, Twitter.com, the sexy starlet vows to keep her ''followers'' abreast of her activities. ''Everyone always says What happens in Vegas, stays in Vegas. not for me! I have my iPhone in hand and have no problem posting all the naughty things I get into before leaving Las Vegas!'' Angelina said. Armanis twitter URL is appropriately enough Twitter.com/XXXSupermodel.
No Vegas vacation for the sexy starlet! Angelina Armani may be in a skimpy bikini by the pool, but that is part of the job for this model-esque babe! Meet her this week in Las Vegas for the XBIZ Summer Forum or follow her sexy exploits on Twitter.com!
All Photos courtesy of Danni.com
For more Angelina Armani, please visit Myspace.com/AngelinaArmani and Twitter.com/xxxSupermodel
To interview Angelina Armani please contact the Star Factory: 818-730-7254 firstname.lastname@example.com
A press release by www.TheStarFactoryEnt.com
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Paralympians 'should have received more honours', says former sports minister as row over 'double standards' escalates
Comments follow the revelations in the Independent on Sunday that leading Paralympians were disappointed at what they called the double standards
Kevin Rawlinson
Kevin Rawlinson is a reporter at The Independent, writing about technology, and social media and protests/riots.
Sunday 30 December 2012
Britain's Paralympians should have received more honours in the Queen's New Year's list, according to the former sports minister Gerry Sutcliffe, who said an opportunity has been missed by overlooking athletes, some of whose gold medal tallies are into double figures after a successful Games.
The comments follow the revelations in the Independent on Sunday that leading Paralympians were disappointed at what they called the double standards which saw all but one Paralympian passed over for the top honours.
Only cyclist Sarah Storey was given the highest award of a dame or knighthood.
"If you remember, at the start of the year there was confusion over whether the Olympians and Paralympians would get honours; the committee said it was unlikely. We managed to get them to change their mind and have a separate category for Olympians and Paralympians," said Mr Sutcliffe.
Speaking to BBC Radio 4's The World This Weekend, he added: "There was an opportunity to be consistent and if you look at his record over several Olympics I think the least he should have got is a knighthood.
"Because the whole purpose of the Games was to inspire a generation - and how better to inspire a generation of Paralympians than to give somebody a knighthood?"
Dressage rider Lee Pearson OBE told The Independent on Sunday this week that he was "disappointed" at not being awarded a knighthood despite a haul of 10 gold medals. He said: "It's the discrepancy that pisses me off.
"Obviously, 10 gold, one silver and one bronze just isn't enough. I'm disappointed because I do feel I've given a lot to Paralympic sport and equestrianism. I think 10 gold medals is quite an achievement."
Wheelchair racer David Weir, who has won six gold medals added: "It's a weird one, how they choose it. Sometimes it seems that Paralympians have to win lots and lots of medals to get a damehood or a knighthood.
"Kelly Holmes was made a dame when she won two gold medals, but it seems we have to get into double figures to get it. Sarah Storey should have been awarded this years ago. I feel that sometimes we are left out, perhaps because we are not in the public eye. It is a bit strange, but I am just honoured to get anything from the Queen for doing a sport I love," he told the Daily Telegraph.
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Costa Sands Resort Pasir Ris
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TripAdvisor Reviews Costa Sands Resort Pasir Ris Singapore
Travel Blogs from Singapore
Over seas from coast to coast...
... it with the not so typical guess 'Russia'! Clearly, they don't get many white people visiting! Anyway, we hopped on the bus and rode til the botanic gardens. They were huge-1/5 the size of Central Park! We didn't walk around the whole park but we made sure to visit the Orchid Garden and spot the local wildlife. We saw dragonflies, a wild chipmunk (I named him Charles) and a cat (I didn't name him)! If we'd had more time we'd have spent more ...
Homeward Bound
Today was our last day in Singapore and we didn't do much. After breakfast at the hotel we went for a walk along the river and then went into a shopping mall where it was much cooler just to pass the time. Marty has pulled a muscle in his leg so walking was very limited today. We had a cold drink for lunch before ambling back to the hotel and resting ...
Mini city - access denied
... open, or at least it looked like it. We asked about ordering pizza's and the lady behind the till promptly turned the advertisement screens off. Apparently they were 'out of stock.' We then asked about the lasagnes that were on another advertisement board and she promptly turned those off as well. All we could order was a very limited amount of cakes and pastries on the shelves, which we did; we managed to get rid of most of the bit of money ...
Singapore - time to meet my work colleagues
... was joining us and we had a nice evening with beer and chilli crab. But I have to say something. They both are living since couple of years in Singapore, but they still need google maps to find their way around. Note: Singapore is not big. So it was really funny ...
Footsteps of Raffles
... tradition throw peanut shells on the floor.Raffles has developed a lot in the 25 years since I was last here. Our afternoon trip finished with a Bum Boat trip down the river to the
Marina Bay where the Merlion spouts water into the bay.
Back to Chinatown for our evening meal - such a choice that we decided just to go to the first we looked at. A really excellent meal in pleasant air conditioned surroundings though we did succumb to the use of a knife and spoon!
Other places to stay in Singapore
Island ResortEast Region, Singapore | Resortfrom $140


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2bed property wanted
Looking for a 2 bed property in or around Weston or Bristol that takes dss rent can't be no higher then 525-550pcm thanks
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nscott (Nick Scott)
Last login: Monday, September 19, 2011
Comment history
Was pinch hitting for Alcides Escobar the right call?
June 9, 2011 at 10:47 a.m. ( permalink | suggest removal )
Kansas City Royals week in review: 5/31/2011
Thanks. I appreciate that. I like the connection to cool hand luke. I still think that a lot of his problems stem from something he does while pitching from the stretch.
May 31, 2011 at 11:10 a.m. ( permalink | suggest removal )
Kansas City Royals week in review: 5/31/2011
I honestly don't get to as many as I'd like. Getting a press credential has helped some, but doing what I do in many ways is better from home in front of a tv. Plus I travel quite a bit and would like to spend some time with my family. That all translates into fewer games than I'd really like. Been to about 3-5 this year. HOpe to triple that at least by the end of the season.
May 31, 2011 at 10:35 a.m. ( permalink | suggest removal )
Kansas City Royals week in review: 5/31/2011
absolutely. This week has to be better, it's almost impossible for it not to be.
May 31, 2011 at 10:27 a.m. ( permalink | suggest removal )
Royals broadcaster and pitcher Paul Splittorff has died
I echo all of your sentiments. My lasting image of him will be sitting alone in the pressbox watching the game and seemingly deep in thought. Little did I know, that two weeks later he would be gone.
May 25, 2011 at 10:17 a.m. ( permalink | suggest removal )
Royals option Jarrod Dyson to Omaha and promote Greg Holland
Oh, I gotcha. sometimes it's hard to tell on the internet.
May 19, 2011 at 11:49 a.m. ( permalink | suggest removal )
Royals option Jarrod Dyson to Omaha and promote Greg Holland
Those mistakes would be more tolerated if the players were well thought of. I don't believe the Royals or Ned Yost send guys down for one mistake. Having guys on pins and needles isn't the best way to run a club. Also the pick-off wasn't completely dysons fault. Feliz was balking.
May 19, 2011 at 11:36 a.m. ( permalink | suggest removal )
Kansas City Royals promote Danny Duffy and insert him into the starting rotation
It's not entirely the pitchers fault, there was a lot of bad luck on that night and things compounded. I think it's certainly debateable as to whether or not Ned Yost shoul'dve pulled him, but I can see both sides.
May 18, 2011 at 9:56 a.m. ( permalink | suggest removal )
Former Royals pitcher Paul Splittorff reportedly fighting cancer
Yes, it certainly is. I hope that he recovers. I've always loved his analysis.
May 16, 2011 at 4:07 p.m. ( permalink | suggest removal )
Royals insert Vin Mazzaro into starting rotation
I have a good feeling about Mazzaro. I think he could be a decent upgrade, or at worst a nice replacement for an injured pitcher. Depth is the one thing I think the Royals bullpen has. In the past they would put a pitcher on the DL and replace him with junk.
May 11, 2011 at 5:34 p.m. ( permalink | suggest removal )
Jack Ellena Honda 785-843-0550
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News Details
Hamilton keen to make improvements
Lewis Hamilton says he is looking forward to working on improvements ahead of the Chinese Grand Prix following his win in Bahrain.Wednesday saw Hamilton testing tyres for Pirelli at the Bahrain International Circuit, meaning he couldn't focus on trying to make any progress with his car ahead of next weekend's race in Shanghai. However, Hamilton said when he gets back to the factory his focus will be on improving on areas where he struggled during the thrilling battle with Nico Rosberg in Bahrain."To be honest I haven't thought about [China] yet," Hamilton said. "Last week is still fresh in my mind, I've got some work to do in the factory this week and I've got to make some...
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In my project (c#), we have an HttpModule that creates a custom Principal that we attach to the CurrentPrincipal.
This is working in all of our MVC3 apps and in our classic ASP.Net apps.
We have an AuthorizeAttribute override we use to secure our Controller methods - seems pretty standard.
The problem is that in the custom authorizeAttribute, the user (httpContext.User) is a RolePrincipal and not the custom principal.
To troubleshoot, I put some handlers in my global.asax to trap beginrequest() and endrequest(). Well, in BeginRequest my User is what we expect - the custom principal. In EndRequest, the user is a RolePrincipal again. The web.config declarations of the HttpModule are good - I can step thru the HttpModule's code.
Does anyone know what's going on? We have a custom HttpModule, but I can't modify that code for this project (it's being used everywhere and it works fine).
This is my first MVC4 project - I'm wondering if MVC4 does something differently.
Code below. Is there any info I've left out?
edit: added authorizationattribute code.
(In HttpModule)
private void BeginRequest(object Sender, EventArgs e)
HttpContext context = HttpContext.Current;
var Id = new TASBIdentity();
context.User = new TASBPrincipal(Id);
Thread.CurrentPrincipal = context.User;
(In global.asax)
void Application_BeginRequest(object sender, EventArgs e)
HttpContext context = HttpContext.Current;
var user = context.User; // user is correct type
void Application_EndRequest(object sender, EventArgs e)
HttpContext context = HttpContext.Current;
var user = context.User; // user is default type (not correct)
(In the authorizeattribute)
public class SecuredByFunctionAttribute : AuthorizeAttribute
private readonly string _functionKey;
public SecuredByFunctionAttribute(string functionKey)
_functionKey = functionKey;
protected override bool AuthorizeCore(System.Web.HttpContextBase httpContext)
return httpContext.User.IsInRole(_functionKey);