HIV SEMINARPHARMACOLOGY

global

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

GLOBAL MODEL OF

HIV 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

General Health Promotion

Specific Protective Measures

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

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 & selectively to CCR5( coreceptor for

entrance of HIV into CD4+ cell)

block entry CCR5-tropic HIV into the 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 inhibitorZidovudine Thymidine

Nonucleoside inhibitorEfavirence

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

INHIBITION OF VIRAL MATURATION

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

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 adolescentGuidelines For The Management Of Adult HIV Infection With Antiretroviral Therapyhttp://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 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)

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??