Pharmacology in HIV
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Transcript of Pharmacology in HIV
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HIV SEMINARPHARMACOLOGY
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global
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Natural history of disease
susceptibility Subclinical disease
Clinical disease
Recovery, disability, death
P r i m a r y p r e v e n ti o n
S e c o n d a r y p r e v e n ti o n
Te r ti a r y p r e v e n ti o n
Exposure Onset of
symptoms
Incubation period
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GLOBAL MODEL OF
HIV PREVENTION
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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
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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
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Primary prevention
General Health Promotion
Specific Protective Measures
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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
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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
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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
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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
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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.
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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
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ANTIRETROVIRAL DRUGS(HIV)
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ATTACHMENT AND ENTRY INHIBITORS
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MOA : MARAVIROC
Maraviroc bind specificity & selectively to CCR5( coreceptor for
entrance of HIV into CD4+ cell)
block entry CCR5-tropic HIV into the cell
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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.
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INHIBITION OF VIRAL GENOME REPLICATION
-nucleoside reverse transcriptase inhibitors (eg: Zidovudine)
-nonnucleoside reverse transcriptase inhibitors (eg : Efavirence)
-HIV integrase inhibitors (eg : Raltegravir)
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MOA: ZIDOVUDINE (NRTIs) and EFAVIRENZ (NNRTIs)
Nucleoside inhibitorZidovudine Thymidine
Nonucleoside inhibitorEfavirence
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MOA : RALTEGRAVIR
Integrase enzyme brings about the
insertion of HIV DNA into human DNA,
thereby helping to hide HIV's DNA inside the
host cell's DNA
1. Raltegravir inhibits integrase2. Inhibit strand transfer
3. Intefere with integration pathway
4. Viral DNA cannot be passed to chromosome host cell’s DNA
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INHIBITION OF VIRAL MATURATION
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MOA : RITONAVIR
The viral maturation is
inhibited
The production of the viral particle
is inhibited
Act as protease inhibitor in which block the action
of protease
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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
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GUIDELINES FOR HIGHLY ACTIVE
ANTIRETROVIRAL THERAPY (HAART):
HOW TO USE THE DRUGS?
Based on:Rapid Advice: antiretroviral therapy for HIV infection in adults and adolescentGuidelines For The Management Of Adult HIV Infection With Antiretroviral Therapyhttp://www.who.int/hiv/pub/arv/rapid_advice_art.pdf
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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.
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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).
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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
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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)
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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
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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
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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
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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
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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
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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
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VACCINE???IS THERE ANY VACCINE AVAILABLE??
IS IT POSSIBLE TO MANUFACTURE ONE??