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HIV SEMINAR
  PHARMACOLOGY
global
N ur al hi st or y of di sease
  at

                                Onset of
       Exposure                symptoms

                  Incubation
                    period
                                                          Recovery,
                   Subclinical             Clinical
susceptibility                                           disability,
                     disease                disease
                                                            death




 Primary                  Secondary                    Te r t i a r y
prevention                prevention                  prevention
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 AIDS
Secondary 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 diseases
Tertiary 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
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
Primary
           prevention


                     Specific
General Health
                    Protective
  Promotion
                    Measures
Specific Protective Measures
1. 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
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
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
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
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.
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
ANTIRETROVIRAL DRUGS
        (HIV)
ATTACHMENT AND ENTRY INHIBITORS
MOA : MARAVIROC




   Maraviroc bind specificity &
                                      block entry CCR5-tropic HIV into
selectively to CCR5( coreceptor for
                                                  the cell
  entrance of HIV into CD4+ cell)
MOA: ENFUVERTIDE
  Enfuvertide interfere with entry HIV-1 into
     host cell by inhibit fusion virus & cell
                   membrane




Viral surface glycoprotein gp120 must bind to
                 host CD4+ cell




 viral glycoprotein gp41 undergoes change in
 shape facilitating fusion of viral membrane
                    with cell




Enfuvertide bind to viral envelope glycoprotein
    & prevent change in shape require for
membrane fusion & viral entry into target cell.
INHIBITION OF VIRAL GENOME
            REPLICATION

  -nucleoside reverse transcriptase inhibitors
                (eg: Zidovudine)
-nonnucleoside reverse transcriptase inhibitors
                 (eg : Efavirence)
   -HIV integrase inhibitors (eg : Raltegravir)
MOA: ZIDOVUDINE (NRTIs) and
              EFAVIRENZ (NNRTIs)
     Nucleoside inhibitor
Zidovudine Thymidine




 Nonucleoside inhibitor
      Efavirence
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,                    pathway
thereby helping to hide
 HIV's DNA inside the     4. Viral DNA cannot be passed to
     host cell's DNA        chromosome host cell’s DNA
INHIBITION OF VIRAL MATURATION
MOA : RITONAVIR

 Act as protease
                     The production of      The viral
inhibitor in which
                      the viral particle   maturation is
 block the action
                        is inhibited        inhibited
   of protease
Class of drug           Adverse effect,contraindication and drug-drug
                        interaction

ENTRY INHIBITOR
Maraviroc               Hepatotoxicity (increase in liver enzymes)
Enfuvertide             Reactions at s.c injection sites
REPLICATION INHIBITOR
Zidovudine              Myelosuppression,lipodystrophy
Efavirenz               CNS effect,Steven Johnson syndrome
Raltegravir             Rhabdomyolysis,myopathy
PROTEASE INHIBITOR
Ritonavir               Peri-oral paraesthesia
GUIDELINES FOR
     HIGHLY ACTIVE
ANTIRETROVIRAL 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
     http://www.who.int/hiv/pub/arv/rapid_advice_art.pdf
HAART?

 Highly active antiretroviral therapy (ART) using 3 or more
active anti HIV drugs from at least 2 different class with the
aim of achieving durable viral suppression to undetectable
       levels, the therapeutic goal under most clinical
                        circumstances.
BEFORE STARTING THE REGIMEN
Therapy is recommended for asymptomatic patients with a CD4 cell count
≤500/μL, for all symptomatic patients, and those with specific conditions and
comorbidities. 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).
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
WHAT TO START?
Principles for selecting the first-line regimen
1. Choose Lamivudine in all regimens
2. 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)
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
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
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
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
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
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
VACCINE???
IS THERE ANY VACCINE AVAILABLE??

IS IT POSSIBLE TO MANUFACTURE ONE??

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Pharmacology in HIV

  • 1. HIV SEMINAR PHARMACOLOGY
  • 3.
  • 4.
  • 5.
  • 6. N ur al hi st or y of di sease at Onset of Exposure symptoms Incubation period Recovery, Subclinical Clinical susceptibility disability, disease disease death Primary Secondary Te r t i a r y prevention prevention prevention
  • 7.
  • 8.
  • 9. 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 AIDS Secondary 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 diseases Tertiary 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
  • 10. 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
  • 11. Primary prevention Specific General Health Protective Promotion Measures
  • 12. Specific Protective Measures 1. 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
  • 13. 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
  • 14. 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
  • 15. 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
  • 16. 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.
  • 17. 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
  • 19.
  • 20. ATTACHMENT AND ENTRY INHIBITORS
  • 21. MOA : MARAVIROC Maraviroc bind specificity & block entry CCR5-tropic HIV into selectively to CCR5( coreceptor for the cell entrance of HIV into CD4+ cell)
  • 22. MOA: ENFUVERTIDE Enfuvertide interfere with entry HIV-1 into host cell by inhibit fusion virus & cell membrane Viral surface glycoprotein gp120 must bind to host CD4+ cell viral glycoprotein gp41 undergoes change in shape facilitating fusion of viral membrane with cell Enfuvertide bind to viral envelope glycoprotein & prevent change in shape require for membrane fusion & viral entry into target cell.
  • 23. INHIBITION OF VIRAL GENOME REPLICATION -nucleoside reverse transcriptase inhibitors (eg: Zidovudine) -nonnucleoside reverse transcriptase inhibitors (eg : Efavirence) -HIV integrase inhibitors (eg : Raltegravir)
  • 24. MOA: ZIDOVUDINE (NRTIs) and EFAVIRENZ (NNRTIs) Nucleoside inhibitor Zidovudine Thymidine Nonucleoside inhibitor Efavirence
  • 25. 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, pathway thereby helping to hide HIV's DNA inside the 4. Viral DNA cannot be passed to host cell's DNA chromosome host cell’s DNA
  • 26. INHIBITION OF VIRAL MATURATION
  • 27. MOA : RITONAVIR Act as protease The production of The viral inhibitor in which the viral particle maturation is block the action is inhibited inhibited of protease
  • 28. Class of drug Adverse effect,contraindication and drug-drug interaction ENTRY INHIBITOR Maraviroc Hepatotoxicity (increase in liver enzymes) Enfuvertide Reactions at s.c injection sites REPLICATION INHIBITOR Zidovudine Myelosuppression,lipodystrophy Efavirenz CNS effect,Steven Johnson syndrome Raltegravir Rhabdomyolysis,myopathy PROTEASE INHIBITOR Ritonavir Peri-oral paraesthesia
  • 29. GUIDELINES FOR HIGHLY ACTIVE ANTIRETROVIRAL 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 http://www.who.int/hiv/pub/arv/rapid_advice_art.pdf
  • 30. HAART? Highly active antiretroviral therapy (ART) using 3 or more active anti HIV drugs from at least 2 different class with the aim of achieving durable viral suppression to undetectable levels, the therapeutic goal under most clinical circumstances.
  • 31. BEFORE STARTING THE REGIMEN Therapy is recommended for asymptomatic patients with a CD4 cell count ≤500/μL, for all symptomatic patients, and those with specific conditions and comorbidities. 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).
  • 32. 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
  • 33. WHAT TO START? Principles for selecting the first-line regimen 1. Choose Lamivudine in all regimens 2. 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)
  • 34. 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
  • 35. 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
  • 36. 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
  • 37. 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
  • 38. 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
  • 39. 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
  • 40. VACCINE??? IS THERE ANY VACCINE AVAILABLE?? IS IT POSSIBLE TO MANUFACTURE ONE??

Notes de l'éditeur

  1. 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
  2. Methadone maintenance therapy (MMT)Provision of anti-retroviral (ARV) treatment in Malaysian prisoners