Definitions n HIV stands for H uman I mmunodeficiency V irus. It is a - - PDF document

Definitions

n HIV stands for Human Immunodeficiency

• Virus. It is a Retrovirus.

n HIV Infection is the state where the virus

is in the body. In most instances this is the asymptomatic state, which is a prelude to AIDS

n AIDS stands for Acquired Immune

Deficiency Syndrome.

n “Acquired” means it is transmissible, and n “Immune-Deficiency” means it damages

the body defense system

n “Syndrome” refers to a group of illnesses

Historical Background of HIV

n 1981 – Doctors in the United States

recognized Pneumocystis Carinii Pneumonia (PCP) in homosexual males,

a condition previously unreported in healthy adults. Later they recognized that all these patients were immunosuppressed.

n 1983/4 – Scientists described the cause

• f this acquired immunodeficiency

syndrome (AIDS) as a retrovirus:

n Lymphadenopathy Associated Virus

(LAV).

n AIDs Associated Retrovirus (ARV). n Human T-lymphotrophic Virus Ш (HTLV-

Ш).

Historical Background of HIV

n 1984– The first case in Kenya was

described

n 1986 – Human Immunodeficiency

Virus (HIV) was accepted as the international designation for

theretrovirus in a WHO consultative meeting

n 1996 – ARVs became available in

the world.

n 1997 – ARVs became available in

the private sector in Kenya.

n 2003 – ARVs became available in

public sector in Kenya.

n 2006 – Approximately 90,000

Kenyans are taking ARV treatment.

Epidemic update Global update

n Estimated 40 million living with

HIV by end of 2005

n About one-third of PLHA are

between 15-24 years

n Most people are still unaware

they are infectedYoung

women are more vulnerable

Adults And Children Estimated To Be Living With HIV As Of End 2005 Children (<15 years) estimated to be living with HIV as of end 2005

Epidemic Update: Sub- Saharan Africa

n HIV is now the leading cause of death n 25.0 – 28.2 million living with HIV

infection by end of 2003

n 10-15% of need ARV n Estimated 3-3.4 million new HIV

infections in 2003

n 70% found in sub Saharan Africa n 10% (600 million) of world’s population

live in sub Saharan African

n By 2010, an estimated 106 million

children under age 15 will have lost

• neor both parents, with 25 million of this

group orphaned due to HIV/AIDS

District estimates are summed to the province and national level(NACC)

National HIV estimates for 2006

Epidemic update: Kenya ..

Epidemiology/Impact of HIV/AIDS in Kenya

n 60% medical beds- HIV/AIDS n 40% Paediatric beds-

HIV/AIDS

n >50% TB patients – HIV

+>25% STI patients – HIV+

n Health workers face both the

medical and social challenges

• f HIV/AIDS on a daily basis

MODES OF TRANSMISSION SUMMARY

n Over the past 2 decades HIV

has spread worldwide with devastating epidemiological consequences particularly in Sub Saharan Africa

n MTCT is the main mode of

transmission of HIV infection to children

n HIV/AIDS is a major cause

• fmorbidity and mortality

Unit 2: Human Immunology & Biology Of HIV

Objectives

n Define the cells involved in the

immune system and their function.

n Know the host immune response

during and after infection.

n Basic HIV structure. n The significance of genetic diversity

and classification of HIV.

n The replication cycle of HIV.

The target sites for antiretroviral drugsComponents of the

Immune System

n Found in blood and tissues n White blood cells (WBC)- key

players in immune response (humoral and cellular)

¨ Macrophages act as clearing cells ¨ Neutrophils attack bacteria ¨ Eosinophils attack helminths (and

mediate allergies)

¨ B-lymphocytes make antibodies ¨ T-lymphocytes

n Responsible for attacking viruses, fungi

and some bacteria

n T helper cells central in orchestrating

function of other immune cells

n T killer cells are able to destroy infected

cells

n How HIV affects the

Immune SystemHIV

attaches to cells of the immune system with special

surface markers called CD4 receptors

n Immune cells with CD4

receptors include:

¨ T-helper Lymphocytes ¨ Macrophages ¨ Monocytes ¨ Dendritic cells ¨ Microglial cells

HIV effect on Immune System

n The hallmark of HIV/AIDS is

profound immunodeficiency as a result depletion of CD4+ T

• lymphocytes. The CD4+ T cell

dysfunction is two fold

¨ Reduction in numbers

¨ Impairment in function

The Biology Of The Human Immunodeficiency Virus

Basic Virology: There are two types of HIV.

n

HIV – 1

¨

Is found worldwide

¨

Is the main cause of the worldwide pandemic

n

HIV – 2

¨

Is mainly found in West Africa, Mozambique and Angola.

¨

Causes a similar illness to HIV – 1

¨

Less efficiently transmissible rarely causing vertical transmission Less aggressive with slower disease progression

Structure Of Human Immunodeficiency Virus

HIV Life Cycle

SUMMARY

n HIV attacks the Immune

system of human being and leads to profound immunodeficiency.

n Rapid replication of HIV

causes genetic diversity of the virus.

n Knowledge of the HIV

structure is important in understanding the mechanismof ARV drugs

UNIT 3:

Natural progression of HIV

Objectives

n Describe stages of HIV

progression - serocoversion, asymptomatic, symptomatic and AIDS phases

n Be able to stage HIV infection

by WHO classification

n Host immune response

during HIV infectionPrimary HIV

Infection

¨ On exposure, there is a 2-4

week period of intense viral replication and widespread dissemination of virus characterized by

n High plasma viral load (RNA) n Rapid decline in CD4 count n In some cases an acute illness

• ccurs

¨ Lasts from 1-2 weeks, but it is rarely

diagnosed

¨ Symptoms if present resemble those

• f other viral illnesses; requires high

index of suspicion

n Symptom resolution with reduction

in plasma viremia due to development of an immune response and antibodies to the virus

Asymptomatic Disease(Latency)

n Patients then enter a stage of

asymptomatic disease phase lasting on average 2-10 years (clinical latency)

n Characterized by gradual decline in CD4

count

¨ Rate depends on viral load

n Long term non-progressors

¨ Rare ¨ >>10-15 year survival without ART ¨ CD4>500; low viral load ¨ Host genetic/immunological or viral factors

may be involved

Symptomatic Disease and AIDS

n Viral load continues to rise causing

¨ Increased demands on immune

system as production of CD4 cells cannot match destructionIncreased susceptibility to common infections (URTI, pneumonia, skin etc)

¨ Late-stage disease is characterized

by a CD4 count <200cells/mm3 and the development of opportunistic infections, selected tumors, wasting, and neurological complications).

Revised WHO Classification Clinical Stages I & II

Revised WHO Classification Clinical Stage III

Revised WHO Classification Clinical Stage IV Selected Symptoms

Conditions where a presumptive diagnosis can be made using clinical signs or simpleinvestigations:

n HIV wasting syndrome n Pneumocystis carinii pneumonia (PCP) n Recurrent severe bacterial pneumonia

n Cryptococcal meningitis n Toxoplasmosis of the brain n Chronic orolabial, genital or anorectal herpes simplex

infection for > 1month

n Kaposi’s sarcoma (KS) n HIV encephalopathy n Extrapulmonary tuberculosis n Cryptosporidiosis, with diarrhea >1 month n Isosporiasis

Conditions where confirmatory diagnostic testing is necessary

n Candidiasis of the esophagus or airways n Cytomegalovirus (CMV) retinitis or disease of organs

(other than liver, spleen, or lymph nodes)

n Non-typhoid salmonella septicemia (NTS) n Lymphoma cerebral or B cell NHL n Invasive cervical carcinoma n Visceral Leishmaniasis n Cryptococcosis (extrapulmonary) n Disseminated non tuberculous mycobacterial infection n Progressive multifocal leukoencephalopathy n Any disseminated endemic mycosis (e.g.

histoplasmosis)

WHO Clinical Staging Pediatric

Stage 1

n Asymptomatic n Persistent generalised

lymphadenopathy (PGL)

WHO Clinical Staging Pediatric

WHO Stage 2

n Unexplained persistent

hepatosplenomegaly

n Papular pruritic eruptions n Extensive wart virus infections n Fungal nail infections n Lineal gingival erythema

WHO Clinical StagingPediatric

WHO Stage 2 , cont’d

n Extensive molluscum contagiosum

infection

n Recurrent oral ulcerations n Unexplained persistent parotid

enlargement

n Herpes zoster n Recurrent or chronic upper

respiratory infection (URI): otitis media, otorrhea, sinsusitis, tonsillitis

WHO Clinical Staging Pediatric

Stage 3

n moderate Unexplained malnutrition not

adequately responding to standard therapyUnexplained persistent diarrhoea (14 days or more)

n Unexplained persistent fever (>37.5OC,

intermittent or constant >1 mo)

n Persistent oral candidiasis (outside 1st 6-

8 weeks of life)

n Oral hairy leukoplakia n Lymph node TB

WHO Clinical Staging Pediatric

Stage 3

n Pulmonary tuberculosis n Severe recurrent presumed bacterial

pneumonia

n Acute necrotizing ulcerative

gingivitis/periodontis

n Symptomatic Lymphoid interstitial

pneumonitis (LIP)

n Unexplained anemia (<8 gm/dL),

neutropenia (<1,000/mm3 ), or chronic thrombocytopenia (<50,000/mm3) for >1

• month. HIV-associated cardiomyopathy or

HIV-related nephropathy

n Chronic HIV-associated lung disease

including bronchiectasis

WHO Clinical Staging Pediatric

Stage 4

n Unexplained severe wasting, or severe

malnutrition not adequately responding to standard therapy

n PCP n Recurrent severe presumed bacterial

infection e.g. empyema, pyomyositis, bone/joint infections, meningitis, but excluding pneumonia

n Chronic herpes simplex infection n Extrapulmonary tuberculosis n Kaposi Sarcoma n Esophageal candidiasis n Candida of trachea, bronchi or lungs n Chronic cryptosporidiosis n Extrapulmonary cryptococcosis,

includingmeningitis

WHO Clinical Staging Pediatric

Stage 4

n Central CNS toxoplasmosis n HIV encephalopathy n CMV infection, retinitis or infection

affecting other organs

n Disseminated endemic mycosis (extra

pulmonary histoplasmosis, coccidiomycosis, pennicilliosis

n Chronic Isosporiasis n Disseminated non-tuberculous

mycobacteria infection

n Acquired HIV-associated fistula n Cerebral or B-cell non-non-Hodgkin's

lymphoma

n Progressive multifocal

leukoencephalopathy

n HIV associated cardiomyopathy and

nephropathy

Summary

n HIV targets the CD4 cell

n Reduction in number of CD4

cells destroys the immune system of the host

n Patients with low CD4 cells are

susceptible to many infections

n All HIV positive patients should

be staged as per WHO classification

UNIT 4: ANTIRETROVIRAL Drugs, Initiation and Monitoring of ARTObjective:

n To describe antiretroviral

therapy, including ARV drugs

and patient management

Types of ARVs and how they work?

Basic Descriptions

ARVs act on the HIV by interfering with its viral life cycle: Types:

• NRTIs – Nucleoside Reverse

transcriptase Inhibitors

• NNRTIs – Non-Nucleoside Reverse

transcriptase Inhibitors

• Protease Inhibitors –Protease

Inhibitors

• Fusion Inhibitors (Not currently in

market)

• Nucleoside Reverse

transcriptase Inhibitors NRTIs

n

NRTIs - inhibiting viral enzyme reverse transcriptase from

completing its cell duties

n

NRTIs pretend to act like a true raw material (nucleotide) for viral RNA development, when it is actually false

n

The false nucleotide (drug) blocks further progress of this step in viral lifecycle

n

Examples are AZT, 3TC, d4T,

• Non-Nucleoside Reverse

transcriptase Inhibitors NNRTIs

n

NNRTIs- viral enzyme reverse transcriptase from completing itscell duties but in a different way from the NRTIs.

n

NNRTIs block the site of assembly of viral raw materials for viral RNA development

n

So even if there are raw materials for viral assembly, they cannot be joined together

n

Examples: NVP, EFV

• Protease Inhibitors PIs

n

Protease Inhibitors-Work by inhibiting division of viral particles to new strands that form new HIV

n

Very potent, expensive drugs,

n

Fewer side effects but may be more serious

Usually not first line drugs – used after others have failed or have bad side effects ............

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