p1 virology, pathogenesis and treatment of hiv infection

P1

Virology, Pathogenesis And Treatment Of HIV Infection

P2

Learning Objectives

• The LT will know what is HIV and the disease burden caused by it? What is AIDS?

• How it is acquired? How it establishes in body? How to prevent getting infected with HIV?

• How HIV causes disease? How the HIV disease progresses (natural history)?

• How the body fights the virus ? Role of CD4 cells

• What effects are produced in the body?

• How the patient is treated? What is ART?

P3

HIV and AIDS

HIV

•HIV is human immunodeficiency virus.

•Two types HIV 1 and HIV 2

•Both have many subtypes

AIDS

•Acquired immune deficiency syndrome- Last stage-HIV disease-CD4 cells less than 200/µ L

•And patient sick with opportunistic infections.

P4

Disease burden due to HIV

There are 33 million HIV infected allover the world.

2.3 to 2.5 million of these are in India

Prevalence of HIV 0.36% in general population amongst people like you and me. Prevalence is higher in high risk groups (CSW,MSM, IDUs, STI cases, migrants, etc where 5-10-20 or more out of 100 may have HIV)

NACP III extremely important to provide care, support, and treatment to HIV positive and prevent new HIV infections

P55

Structure of HIV

P6

1. Sexual Transmission (vaginal, anal, oral) Heterosexual (most common in India)Homosexual

2. Blood Contact Blood and blood products transfusions Intravenous drug use Occupational exposure (needle stick, cuts etc.)

3. Mother-to-Child During pregnancy During delivery Breast Feeding

Routes/Mechanisms of Transmission

P7

•Sexual Transmission: Safe sexual practices, using condoms etc.

•Transmission through blood and blood products: Ensure screened blood and blood products are used (Safe blood and blood products, rationale use of blood)

•Through needles (IDUs), needle stick and occupational exposure: standard work precautions and PEP (safe needles including for IDUs)

•HIV positive mother to the baby: PPTCT program

Prevention of HIV Transmission

P8

Susceptibility of HIV

HIV is a highly fragile virus. Needs living cells to survive. The methods used for sterilization and disinfection to kill the virus.

• Autoclaving at 1210C at 15 lb pressure for 20 minutes

• Dry heat 1600C for 1 hr. (holding time)

• Boiling for 20 minutes

• Sodium hypochlorite 1% (routine) 10% (spill)

• Ethanol 70%

• Povidone iodine (PVI) – 10%

• Glutaraldehyde (activated) 2% for 30 minutes

8

P99

HIV Pathophysiology - Life Cycle

CD4 cell

P10

Step One: Attachment

P1111


CD4

Co-receptor(CCR5 or CXCR4)

CD4 Binding

P12


FUSION

P13


Virion entry

P14


HIV RNA

P15


Reverse transcription

HIV DNA

P16


Translocation to nucleus

P17


Integration

P18


Transcription / Translationof HIV mRNA / polyprotein

P19


Protease processingand viral assembly

P20

Normal Defense Of Body And Host Response To HIV Infection (Natural

History Of HIV Infection)

P21

lymphocytesmonocytes

eosinophils

basophils

erythrocytes

platelets

Various Blood Components

P22

Normal body defenses and HIV

The body’s normal defenses are:

•B cell: humoral immunity antibodies

•T Cell population: CMI - CD4 – helper T

CD8 – cytolytic T cell

HIV targets these defenses, primarily attacking CD4 cells. CD4 cells are

progressively lost during the course HIV disease (in the absence of

treatment) leading to continuous viral replication and increased

opportunistic infections.

P23

Window period

Time taken from day of HIV infection to positive HIV antibody test (ELISA/RAPID)

Most HIV infected seroconvert within six months

P24

24

AIDSClinical latencyAcute HIV Infection

Natural History of HIV-1 Infection Progressing to AIDS*

1-12 weeks 6-10 years 1-2 years

Vir

al L

oad

C

D4

cell

leve

l

Acute HIV infection

Clinical latency

AIDS

6-12weeks 6-11 years1-2 years

*Without ART

P26

Rate of progression of HIV infection without ART

Based on kinetics of virologic and immunologic events three dominant patterns of HIV disease are described.

1. 80-90% of HIV infected are typical progressors survival time appx. 11 years.

2. 5-10 are “rapid progressors” with median survival time of 3-4 years.

3. 7-10% of HIV-infected individuals do not experience disease progression for extended period of time and are called “long term non progressors” (LTNPs).

P27

Life Cycle and ARVs site of action

ReverseTranscriptaseInhibitors(12)

ProteaseInhibitors(7)

Fusion/EntryInhibitors (1)

IntegrationInhibitors

P28

ART works: Progression to AIDS/Death

30

20

105

0

25

15

1 2 3 4 5 6 7 8 9 10 11 12 13

No Therapy

Mono-Therapy

Dual Therapy

Triple Therapy

Months

% P

atie

nts

Pro

gre

ssin

g

JAMA 1998

p1 virology, pathogenesis and treatment of hiv infection

Documents