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Natural Course of HIV Infection

HAIVNHarvard Medical School AIDS

Initiative in Vietnam

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By the end of this session, participants will be able to:

Explain the process that HIV infect the human cell

Describe the natural progression of HIV infection

Explain the factors that influence the progression of HIV infection

Identify the clinical stage according to the World Health Organization (WHO)

Learning Objectives

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How Does HIV Infect the Human Cell?

HIV Life Cycle

CD4

CD4

Co-receptor CCR5 và CXCR4

CD4 Binding

HIV Life Cycle

Fusion

HIV Life Cycle

Virion Entry

HIV RNA

HIV Life Cycle

Reverse transcription

HIV DNA

HIV Life Cycle

Translocation to nucleus

HIV Life Cycle

Integration

HIV Life Cycle

Transcription / Translation of HIV mRNA / polyprotein

HIV Life Cycle

Protease processingand viral assembly

HIV Life Cycle

New Virus Released

Vòng đời của HIV

HIV Life Cycle & Mechanism of ARV

ReverseTranscriptaseInhibitors(14)

ProteaseInhibitors(10)

Fusion/Entry

Inhibitors (2)

IntegrationInhibitors(1)

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HIV test identifies antibodies to the HIV virus in the blood

HIV test become positive after HIV infection 1-3 months

Results of two additional HIV tests should be confirmed positive before diagnosis of HIV infection

Xét nghiệm HIV

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Antibody testsRapid ELISA / Rapid EIA (“Rapid test”): • Results in 10 minutes to 2 hours • Positive results must be confirmed with

additional testingWestern Blot (WB)• Used as a confirmatory test

Dry Blood Spot(DBS):• Used for early HIV diagnosis for infants by

PCR at 4-6 weeks of age

Các phương pháp xét nghiệm HIV

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Two common tests used to assess and monitor HIV patients are:

CD4 count

Total lymphocyte count (TLC)

Testing in HIV patient

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Plasma HIV RNA levels indicate:• the magnitude of HIV replication and • the rate of destruction of CD4+ cells

CD4 and T cell counts indicate the extent of HIV-induced immune damage already suffered

CD4 Count and Viral Load Testing

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Relationship Between CD4 Counts and HIV Viral Load

Slow: <10,000, Fast: >100,000

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Natural Progression of HIV Disease

0

100

200

300

400

500

600

700

800

900

1000

0 1 2 3 4 5 1 2 3 4 5 6 7 8 9 10 11

CD

4+

ce

ll C

ou

nt

AsymptomaticAsymptomatic

HZVHZV

OHLOHL

OCOCPPEPPE

PCPPCP

CMV, MACCMV, MACTBTB

TBTB

Months Years After HIV Infection

Acute HIVAcute HIVinfectioninfectionsyndromesyndrome

Relative level of Plasma HIV-RNA

CD4+ T cells

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CD4

5yrs 10yrs 15yrs

500

200

Long term non-progression

Rapid progressionDeath

Death

OI OI

Typical Progression

Variable Progression of HIV infection

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HIV progresses through various stages which include:

1. Primary HIV Infection

2. Latent Period

3. AIDS (advanced HIV Infection)

Diễn biến tự nhiên của nhiễm HIV

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Occurs 2-4 weeks after acquiring HIV infection

Symptoms last 1-2 weeks In the US and Europe, 53-93% of

patients have symptoms In Vietnam and development

country, there’s no data about incidence

Primary HIV Infection (1)Incidence

Symptoms Rate

Fever 95%

Muscle/ joint pain 80%

Lymphadenopathy 75%

Pharyngitis 75%

Rash 70%

Nausea/vomiting/diarrhea 30-60%

Headache 33%

Primary HIV Infection:Clinical Manifestations

The Sanford Guide to HIV/AIDS Therapy 2005

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A generalized rash is a common finding:• 5-10 mm macular or papular

erythematous lesions • appears 48-72 hours after fever starts• lasts for 5 – 8 days• most often involves the face and trunk• typically not pruritic• can be accompanied by oral, esophagus,

anus and genital ulcerations

Primary HIV InfectionRash(1)

Primary HIV Infection:Rash (2)

Primary HIV Infection:Pharyngitis

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Characterized by gradual decline in CD4 count

Patients may be healthy for 5-10 years before symptoms develop

Symptoms can develop when CD4 < 500 cells/mm3

OIs develop when CD4 < 200 cells/mm3

Latent Period: Asymptomatic HIV Disease

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Generally occurs when CD4 < 500 Conditions that may be seen when

CD4 count is 200 – 500 include:• Generalized lymphadenopathy• Prolonged fevers or diarrhea for > 1

month• Oral candidiasis• Pulmonary tuberculosis• Herpes zoster (Zona)• Vaginal candidiasis

Latent Period: Symptomatic HIV Infection

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AIDS (Advanced HIV Infection)

Criteria for DiagnosisAdvanced HIV Infection

Any condition under clinical stage 3 or 4 (presumptive or definitive diagnosis)

and/or

CD4 cell count < 350 cells/mm3

AIDS Any condition under clinical stage 4 (presumptive or definitive diagnosis)

orCD4 cell count < 200 cells/mm3

Final stage in the natural progression of HIV Infection

Guidelines for the Diagnosis and Treatment of HIV/AIDS. Ministry of Health, 2009.

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Manifestations of HIV Infection Vary Greatly

Some patients with CD4 > 200 can be ill with many symptoms

Some patients with low CD4 < 100 can feel healthy with no symptoms at all

All patients have decreased immune function and are at risk for OIs when:• WHO Clinical Stage

3 or 4, • CD4 < 200 • TLC < 1200

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What Factors Affect the Rate of Disease Progression?

Speeds disease progression:• Age• Symptoms during

primary HIV• Nutritional status• Opportunistic

infections (eg: TB)• High viral load• Intravenous drug

use?

Slows disease progression: • OI Prophylaxis with

cotrimoxazole• Antiretroviral

Therapy

Antiviral Therapy (ART) and HIV Progression

No ARV1 ARV

2 ARV

3 ARV

% O

f p

atie

nts

did

no

t sh

ow

AID

S

or

dea

th

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WHO Clinical Stages

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WHO Clinical Stage can be used to: Estimate degree of damage done to

a patient’s immune system Follow progression of HIV disease Determine when to start:• prophylactic treatment with cotrimoxazole

• antiretroviral therapy (ART)(with or without CD4 count)

Giai đoạn lâm sàng theo TCTYTG

WHO Clinical Stage should be evaluated at every clinic visit

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Most typical/common syndromes:• Asymptomatic• Persistent generalized

lymphadenophathy

Performance Scale 1: No symtom, Normal activity

Stage 1: Asymptomatic

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Most typical/common syndromes:• Moderate unexplained weight loss (<

10% of body weight)• Recurrent respiratory infections• Zona (Herpes zoster)• Papular pruritic eruption (PPE)

Performance Scale 2: symptomatic but normal activity

Stage 2: Mildly Symptomatic

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Most typical/common syndromes:• severe weight loss (> 10% of body

weight)• chronic diarrhea for > 1 month• Recurrent oral candidiasis• Pulmonary tuberculosis

Performance Scale 3: symptomatic, in bed < 50% of the time

Stage 3: Progressively Symptomatic

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Most typical/common syndromes:• Wasting syndrome due to HIV

weight loss> 10% chronic diarrhea unexplained> 1 month prolonged fever unexplained > 1 month

• OIs Performance Scale 4 : bedridden>

50% of the time

Stage 4: Severely Symptomatic

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Primary HIV Infection phase have very high risk of infection although the test result is usually negative

On average, it takes 5-10 years from time of initial HIV infection to become ill or have symptoms

AIDS is defined as CD4 <200 or stage 4 according to WHO Clinical Stages

CD4 is the best tests to evaluate immune system status

Key Points

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Thank you!

Question?