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
HIV Pathophysiology - Life Cycle
CD4
Co-receptor(CCR5 or CXCR4)
CD4 Binding
P12
HIV Pathophysiology - Life Cycle
FUSION
P13
HIV Pathophysiology - Life Cycle
Virion entry
P14
HIV Pathophysiology - Life Cycle
HIV RNA
P15
HIV Pathophysiology - Life Cycle
Reverse transcription
HIV DNA
P16
HIV Pathophysiology - Life Cycle
Translocation to nucleus
P17
HIV Pathophysiology - Life Cycle
Integration
P18
HIV Pathophysiology - Life Cycle
Transcription / Translationof HIV mRNA / polyprotein
P19
HIV Pathophysiology - Life Cycle
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
P2525
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