Pharmacology in HIV


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this is a topic that i present in one of the seminar in my university..if you find it useful, do not hesitate to download it..thanks!

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  • Why this is important?? There is high prevalence of HIV/AIDS among prisoners than the general public.Factors:Practice of drug injectionsSex among prisoner, whether consensual or forcedPracticed of tattooing or skin piercingLack of education, information and medical care, overcrowding
  • Methadone maintenance therapy (MMT)Provision of anti-retroviral (ARV) treatment in Malaysian prisoners
  • Pharmacology in HIV

    2. 2. global
    3. 3. N ur al hi st or y of di sease at Onset of Exposure symptoms Incubation period Recovery, Subclinical Clinicalsusceptibility disability, disease disease death Primary Secondary Te r t i a r yprevention prevention prevention
    4. 4. Primary Prevention• Encourage the use of condoms and promotion of proper use• Increase information and prevention of HIV and other STI.• Conduct training and awareness activities for HIV/AIDS and other STI• Contribute to the improvement of the information on HIV and sexual health through various media• Promote condom and hydro soluble lubricant use as a prevention method• Elaborate informative materials on HIV prevention• Gather written and audiovisual information on initiative studies and process experiences in HIV• Increase public awareness of the epidemic and disseminate information about AIDSSecondary Prevention• Encourage the early detection of HIV/AIDS and other STI• Encourage the early detection of HIV/AIDS and other STI in the affected person’s contacts• Offer medical testing services for the detection of HIV and opportunistic diseasesTertiary Prevention• Ensure referral to medical services of individuals with positive diagnosis• Provide information and advice on economic, training, social and legal aid.• Provide information and advice on mental health issues• Promote human rights, equality and liberty using cultural mediation• Develop mutual help groups of peers and encourage creation of social networks• Training of health and employment specialists• Encourage and foster support for individuals with HIV regardless of their gender• Promote and foster reintegration for seropositive individuals without economic resources• Organize events with broad social impact and including the media (combat stigmatization and achieve normalization)• Contribute to the change of attitudes on treatment adherence and safe sex
    5. 5. Malaysia National Strategy• National Strategic Plan on HIV and AIDS• National Strategic Plan on HIV and AIDS 2006- 2010• National Strategic Plan on HIV and AIDS 2011- 2015
    6. 6. Primary prevention SpecificGeneral Health Protective Promotion Measures
    7. 7. Specific Protective Measures1. Pilot harm reduction projects – Needle and syringe programmes (NSPs) – Opiod substitution therapy (OST) and other drug dependence treatment – Antiretroviral therapy (ART) – Prevention and treatment of sexually transmitted infections (STIs) – Condom programmes for people who inject drugs (PWID) and their sexual partners – Targeted information, education and communication for PWID and their sexual partners
    8. 8. 2. Comprehensive package for HIV care among Malaysian prisoners• Provision of antiretroviral treatment• Treatment for other HIV related opportunistic infections• HIV/AIDS education and training for prison staff
    9. 9. 3. Mother-to-child transmission (PMTCT) Programme – Antiretroviral (ARV) prophylaxis for the mother during pregnancy and labour and for the infant during the neonatal period – Obstetric interventions to avoid infant exposure to infected maternal secretions – Complete avoidance of breast feeding
    10. 10. SECONDARY PREVENTION• Prevent before progressing further through early detection and intervention• To reduce the prevalence of disease and disability• To cure patient and reduce serious consequences
    11. 11. TERTIARY PREVENTION• Reduce social, religious, cultural, gender, economic, legal and political barriers that make people vulnerable to HIV/AIDS• Increase access to care, support and treatment for people infected, and support for those affected by HIV/AIDS.
    12. 12. Key challenges• The rise in sexual transmission• Sustainability of human, financial and infrastructure resources• Financial cost of providing increased ARV treatment coverage• Mobilizing most at risk populations and vulnerable populations to access public HIV healthcare services• Stigma and discrimination
    15. 15. MOA : MARAVIROC Maraviroc bind specificity & block entry CCR5-tropic HIV intoselectively to CCR5( coreceptor for the cell entrance of HIV into CD4+ cell)
    16. 16. MOA: ENFUVERTIDE Enfuvertide interfere with entry HIV-1 into host cell by inhibit fusion virus & cell membraneViral surface glycoprotein gp120 must bind to host CD4+ cell viral glycoprotein gp41 undergoes change in shape facilitating fusion of viral membrane with cellEnfuvertide bind to viral envelope glycoprotein & prevent change in shape require formembrane fusion & viral entry into target cell.
    17. 17. INHIBITION OF VIRAL GENOME REPLICATION -nucleoside reverse transcriptase inhibitors (eg: Zidovudine)-nonnucleoside reverse transcriptase inhibitors (eg : Efavirence) -HIV integrase inhibitors (eg : Raltegravir)
    18. 18. MOA: ZIDOVUDINE (NRTIs) and EFAVIRENZ (NNRTIs) Nucleoside inhibitorZidovudine Thymidine Nonucleoside inhibitor Efavirence
    19. 19. MOA : RALTEGRAVIR 1. Raltegravir inhibits integrase Integrase enzyme brings about the 2. Inhibit strand transfer insertion of HIV DNA 3. Intefere with integration into human DNA, pathwaythereby helping to hide HIVs DNA inside the 4. Viral DNA cannot be passed to host cells DNA chromosome host cell’s DNA
    21. 21. MOA : RITONAVIR Act as protease The production of The viralinhibitor in which the viral particle maturation is block the action is inhibited inhibited of protease
    22. 22. Class of drug Adverse effect,contraindication and drug-drug interactionENTRY INHIBITORMaraviroc Hepatotoxicity (increase in liver enzymes)Enfuvertide Reactions at s.c injection sitesREPLICATION INHIBITORZidovudine Myelosuppression,lipodystrophyEfavirenz CNS effect,Steven Johnson syndromeRaltegravir Rhabdomyolysis,myopathyPROTEASE INHIBITORRitonavir Peri-oral paraesthesia
    23. 23. GUIDELINES FOR HIGHLY ACTIVEANTIRETROVIRAL THERAPY (HAART): HOW TO USE THE DRUGS? Based on: Rapid Advice: antiretroviral therapy for HIV infection in adults and adolescent Guidelines For The Management Of Adult HIV Infection With Antiretroviral Therapy
    24. 24. HAART? Highly active antiretroviral therapy (ART) using 3 or moreactive anti HIV drugs from at least 2 different class with theaim of achieving durable viral suppression to undetectable levels, the therapeutic goal under most clinical circumstances.
    25. 25. BEFORE STARTING THE REGIMENTherapy is recommended for asymptomatic patients with a CD4 cell count≤500/μL, for all symptomatic patients, and those with specific conditions andcomorbidities. History of the patient are taken,such as Have you been on meds before. Do you have any resistance to medications. What is your current CD4 and viral load counts Are you able to take meds several times each day or do you need a once per day regimen(since the drug have side effects,we need to know whether the patient could endure during the regimen). Are you pregnant or thinking of becoming pregnant What other illnesses and conditions do you have? Start testing the patient whether the patients have already develop any resistance towards drugs in the regimen( for patients that switch towards another regimen).
    26. 26. WHEN TO START?• START ART in all HIV patients who have CD4 count <350 cells/mm3 irrespective of clinical symptoms• CD4 testing is required to identify if patients with HIV and WHO clinical stage 1 or 2* disease need to start antiretroviral treatment• Start antiretroviral treatment in all patients with HIV and WHO clinical stage 3 or 4* irrespective of CD4 count*please refer clinical staging table
    27. 27. WHAT TO START?Principles for selecting the first-line regimen1. Choose Lamivudine in all regimens2. Choose one NRTI to combine with Lamivudine (Zidovudine or Tenofovir or Stavudine)(1 NRTI + 1 NRTI = 2NRTIs = BACKBONE)3. Choose one NNRTI (Neviparine or Efavirenz)For example:• Zidovudine (NRTI) + Lamivudine (NRTI) + Efavirenz (NNRTI)• Zidovudine(NRTI) + Lamivudine (NRTI) + Nevirapine (NNRTI)• Tenofovir (NRTI) + Lamivudine (NRTI) or Emtricitabine (NRTI) + Efavirenz(NNRTI)• Tenofovir (NRTI) + Lamivudine (NRTI) or Emtricitabine (NRTI) + Nevirapine (NNRTI)
    28. 28. ART FOR HIV/TB CO-INFECTION• Start ART in all HIV-infected individuals with active tuberculosis (TB) irrespective of CD4 cell count• Start TB treatment FIRST, followed by ART as soon as possible after starting TB treatment• Use efavirenz as the preferred NNRTI in patients starting ART while on TB treatment. Why??? Hint: TB drugs
    29. 29. ART FOR HIV/HBV CO-INFECTION• Start ART in all HIV/HBV co-infected individuals who require treatment for their HBV infection, irrespective of CD4 cell count or WHO clinical stage• Start tenofovir and lamivudine or emtricitabine (2 NRTIs = BACKBONE) containing antiretroviral regimens in all HIV/HbV co-infected individuals needing treatment
    30. 30. ART FOR PREGNANT WOMEN• Start ART in all pregnant women with HIV and CD4 count <350 cells/mm3, irrespective of clinical symptoms• CD4 testing is required to identify if pregnant women with HIV and WHO clinical stage 1 or 2* disease need to start antiretroviral treatment or prophylaxis• Start ART in all pregnant women with HIV and WHO clinical stage 3 or 4*, irrespective of CD4 count• Start ONE the ART regimens in ART-naive pregnant women eligible for treatment• DO NOT start efavirenz during the first-trimester of pregnancy. Why??*please refer clinical staging table
    31. 31. WHEN TO SWITCH ART• Where available, use viral load (VL) to confirm treatment failure.• Where routinely available, use VL every 6 months to detect viral replication• A persistent VL above 5 000 copies/ml CONFIRMS treatment failure• When VL is not available, use immunological criteria (<100cells/mm3 or return to/below the pretherapy baseline CD4 count) to confirm clinical failure
    32. 32. SECOND-LINE ART• Boosted protease inhibitors (PI) eg. Atazanavir and Ritonavir, plus two nucleoside analogues (NRTIs) are recommended for second-line ART• Simplification of second NRTI options is recommended: 1. If Stavudine or Zidovudine “backbone” has been used in first-line, use Tenofovir + Lamivudine as the NRTI backbone in second-line 2. If Tenofovir “backbone” has been used in first-line, use Zidovudine + Lamivudine as the NRTI backbone in second-line
    33. 33. THIRD-LINE REGIMENS• National programmes should develop policies for third-line therapy that consider funding, sustainability and the provision of equitable access to ART• Third-line regimens should include new drugs likely to have anti HIV activity such as integrase inhibitors (eg. Raltegravir) and second generation NNRTIs (eg. Etravirine) and PIs (eg. Darunavir)• Patients on a failing second-line regimen with no new antiretroviral options, should continue with a tolerated regimen