HIV CLINICAL PICTURE

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Dr. W.C. Lwabby (MMed, MD) Lecturer - Int.
Med.Dept

• HIV CLINICAL PICTURE AND DIAGNOSIS

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Learning Objectives

• To define HIV/AIDS
• To describe the structure and the life cycle of
  HIV
• To describe the burden of the disease
• To describe the ways of transmission
• To describe the diagnosis of the disease

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What is HIV?

• Human
• Immunodeficiency
• Virus
• It spreads through body fluids
• It affects specific cells of the immune system,
• CD4 cells, or T cells
• It kills the bodys CD4 cells (T cells)
• damages the immune system
• It replicates inside the human body
• It must invade a healthy cell in the body to
  survive

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What is AIDS?

• AIDS is a late stage of the HIV infection
• Once diagnosed, body has hard time fighting
  disease and certain cancers.
• NO cure for AIDS, but there is treatment

Diagnosis
Positive HIV Test
Very low CD4 count (lt200 cells) OR
presence of specific cancers or infections
AIDS
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Why this important?
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History of HIV

• The HIV virus first came to light during the
  early 1980s
• A number of healthy gay men in New York began to
  develop rare opportunistic infections cancers,
• that were resistant to treatment
• One such viral opportunistic infection is
  cytomegalovirus
• that causes blindness inflammation of the
  colon

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History of HIV

• Research teams in the U.S.A France
• made independent research discoveries of the
  virus
• French researchers
• Discovered a virus linked to AIDS in 1983,
• They called it Lymphadenopathy-Associated Virus
  (LAV)
• In 1984, American researchers
• Isolated a virus that caused AIDS, calling it
  Human T-lymph tropic Virus type III (HTLV- III)
• These two viruses were later found to be the same
  virus HIV

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History of HIV.

• The emergence of HIV AIDS
• has resulted in countless debates as to where it
  originated from
• It is suspected that it originated from
• S.I.V (Simian Immunodeficiency Virus) which
  affects monkeys

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History of HIV.

• Certain strains of SIV closely resemble the two
  types of HIV
• In 1999
• SIVcpz closely related to HIV1 originated from
  chimpanzees
• HIV2 closely related to SIVsm Originated from the
  green monkey

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STRUCTURE OF HIV
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Retroviral Genes

• Gag (group-specific antigen)
• makes the cone shape viral capsid
• Pol (polymerase)
• codes for viral enzymes reverse transcriptase,
  integrase, and viral protease
• Env (envelope)
• makes surface protein gp120 and trans membrane
  gp41, enabling HIV to fuse to CD4 cells

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• Other genes 
• tat - The Trans activator gene influences the
  function of genes some distance away
• It controls transactivation of all HIV proteins
• rev - The differential regulator of expression
  of virus protein genes

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• vif - The virus infectivity factor gene is
  required for infectivity as cell-free virus
• nef - The negative regulator factor retards HIV
  replication
• vpr - The virus protein R gene has an
  undetermined function

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Types of HIV

• There are two types HIV HIV-1 and HIV-2.
• HIV-1
• Is the virus that was initially discovered
• It is more virulent and more infective
• It causes majority of HIV infections globally
• HIV-2
• Is less virulent
• Is largely confined to West Africa

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Resistance

• The virus are inactivated
• in 10 minutes at 60 centigrade
• in seconds at 100 centigrade
• At room temperature survive for seven days
• HIV are inactivated in 10 minutes by treatment
  with
• 50 ethanol ,35 Isopropanol.
• 0.5 Lysol and paraformaldehyde 0.3, hydrogen
  10
• house hold bleach Hypochlorite solution at 0.5
  2 Glutaraldehyde

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HIV Replication 

• Attachment
• Penetration
• Uncoating
• Reverse Transcription
• Integration
• Replication
• Assembly
• Release

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Infection spread throughout the Body

• Within the inflammatory cells of the infection (T
  cells)
• Site of replication shifts to lymphoid tissues
• Lymph nodes
• Spleen
• Liver
• Bone marrow
• Macrophages and Langerhans cells become
  reservoirs and sites of replication but do not
  die themselves

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Effects of HIV on the immune system

• 1. Destruction of CD4 T cells population
• 2. Immune defect due to HIV infection
• 3. Progression of HIV infection to AIDS

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Hosts immune responses

• Both humoral and cell-mediated immune responses
  partially control the viral production
• infected CD4T cells are destroyed,
• leading to a gradual decline of CD4 T cells
• Antibodies that recognize a variety of HIV
  antigens are produced
• Antibody dependent cell-mediated cytotoxicity
• Apoptosis of infected cells occurs

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Body fluids that contain High concentration of
Viral particles 

• Blood
• Semen/Vaginal fluids (as high as blood)
• Breast milk
• Pus from sores

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Low concentrations of HIV

• It is highly unlikely to be infected when come
  into contact with
• Sweat
• Tears
• Urine
• Saliva (highly possible if blood from mouth sores
  is present)

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High Risk Populations

• Males (homosexuals )
• IV drug users
• Improperly screened transfusion recipients
• Sexual partners of persons infected with HIV
• Infants of HIV infected mothers

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How is HIV Spread?

• HIV is passed from person to person through the
  exchange of bodily fluids.
• 3 Main Ways
• Unprotected sex with people living with HIV
  (vaginal, oral, or anal)
• Blood to blood contact
• Exposure to HIV before or during birth or through
  breastfeeding.

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Symptoms of HIV

• Many people who are infected with HIV have NO
  symptoms at all for 10 years or more.
• Symptoms vary
• Some people who are infected with HIV report
  having flu-like symptoms 2-4 weeks after
  exposure
• Fever
• Enlarged lymph nodes
• Sore throat
• Rash

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Stages of HIV Infection

• A Viral Transmission
• - HIV infection is acquired primarily by
  sexual intercourse
• - Exposure to contaminated blood
• The risk of transmission after a single
  encounter with an HIV source has been estimated
  to be
• - 1 in 150 with needle sharing
• - 1 in 300 with occupational percutaneous
  exposure
• - 1 in 300- 1000 with receptive anal
  intercourse

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• 1 in 500 1250 with receptive vaginal
  intercourse,
• 1 in 1000 3000 with insertive vaginal
  intercourse
• 1 in 3000 with insertive anal intercourse
• Transmission risk increases
• With the number of encounters
• When the source of infection has higher HIV RNA
  plasma levels

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• B Acute ( Primary) HIV infection
• It occurs 1- 4 weeks after transmission
• Is accompanied by burst of viral replication with
  a decline in CD4 cell count
• Is confirmed by demonstrating a high HIV RNA in
  the absence of HIV antibody

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• C Seroconversion
• Development of a positive HIV antibody test.
• Usually occurs within 4 weeks of acute
  infections,
• invariably ( with few exceptions) by 6months
• D Asymptomatic HIV infection
• It lasts a variable amount of time ( 8 10 yrs)
• Is accompanied by a gradual decline in CD4 cell
  counts and relatively stable HIV RNA level.

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E Early symptomatic HIV Infection

• Previously referred to as AIDS Related Complex
• Findings includes
• Thrush or vaginal candidiasis ( persistent,
  frequent or poorly responsive to treatment)
• Herpes zoster( recurrent episodes or involving
  multiple dermatomes)
• Oral leukoplakia
• Peripheral neuropathy
• Diarrhoea
• Constitutional symptoms ( low grade fevers,
  weight loss)

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• FAIDS
• Is defined by a CD4 cell count lt 200/mm3
• CD4 cell percentage of total lymphocytes lt 14,
  or
• one of several AIDS related opportunistic
  infections
• G Advanced HIV Disease
• Corresponds with a CD4 cell counts lt 50/mm3.
• Most AIDS related death occurs at this point.
• Common late stage opportunistic infections are
  caused by CMV disease( retinitis, colitis) or
  Disseminated Mycobacterium avium complex (
  MAC)

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WINDOW PERIOD

• The period of time after HIV infection exposure,
  but before a test can detect it (at least 3
  months)
• Antibody tests cannot accurately identify
  infection during this time.

• Incubation period-
• Time from exposure to HIV to time when
  antibodies can be detected through an HIV test.

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HIV/AIDS DIAGNOSIS

• CLINICAL DIAGNOSIS
• NON SPECIFIC CLINICAL FEATURES OF PRIMARY
  INFECTION
• It is asymptomatic stage in 70-80 of patients
• Usually occurs 2-6 weeks(peak 4-8wks) after
  exposure

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• MAJOR CLINICAL FEATURES
• Fever with rash
• Pharyngitis with cervical lymphadenopathy
• Myalgia/Arthragia
• Mucosal ulceration
• Headache

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• RARELY Usually HIV-RNA levels is above 1 million
  copies/mil (4-8weeks post infection)
• Aseptic meningitis
• Encephalitis
• Myelitis
• Polyneuritis

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HIV SYMPTOMATIC DISEASE

• Oral hairy leucoplakia
• Recurrent oropharyngeal candidiasis
• Recurrent vaginal candidiasis
• Severe pelvic inflammatory disease(severe PID)
• Bacillary angiomatosis
• Herpes zoster

• Cervical dysplasia
• Idiopathic thrombocytopenia purpura
• Weight loss
• Chronic diarrhea
• Peripheral neuropathy
• Low grade fever/night sweat 

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AIDS DEFINING DISEASE

• Esophageal candidiasis
• Cryptococcal meningitis
• Chronic cryptosporidium diarrhea
• CMV renitis/colitis
• Chronic mucocuteneous herpes simplex
• PTB or EPTB
• PCP
• Karposis sarcoma
• Cerebral toxoplasmosis

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• Primary cerebral lymphoma
• Disseminated mycobacterium avium intracellurae
• Progressive multifocal leucoencephalopathy(PML)
• HIV associated wasting
• HIV associated dementia

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• Extrapulmonary histoplasmosis
• Extrapulmonary coccidiodomycosis
• Invasive cervical cancer
• Recurrent non typhi salmonella septicemia

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LABORATORY DIAGNOSIS OF HIV

• HIV can be detected through
• Appearance of specific Anti-HIV antibodies in
  serum(usually 4-12weeks post exposure)
• The test is eligible in 18months of age and above
• Detection of HIV-RNA in serum(ELISA) Can be
  done at any age

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• INTERPRETATION OF RESULT
• Should read after 10-15 min
• One line to control- shows negative result
• Two line/three at control (C) and test (T)-shows
  positive results
• NO line at either C or T-shows invalid test
• NOTE ALL PROCEDURE TO BE DONE UNDER PROVIDER
  INITIATIVE TREATMENT and COUNSELLING (PITC)

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Modality of Immunological Test
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What does the HIV Test Mean?

• Positive

• Negative
• -

• HIV antibodies present
• Infected and can infect others
• Need to begin treatment

• No HIV antibodies detected
• May not be infected (consider the window period)
• Consider retesting

Sunday, February 17, 2019
DR.W.C.LWABBY -HKMU MMED IM
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Viral Load CD4 (T4) Count
Viral Load Amount of HIV in the blood

• CD4 (T4) Count Number of white blood cells in
  the blood

Sunday, February 17, 2019
DR.W.C.LWABBY -HKMU MMED IM
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WHO STAGING

• Stage 1  
• Short, flu-like illness
• Occurs one to six weeks after infection
• No symptoms at all
• Infected person can infect other people
• Persistency generalized lymphadenopathy

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Stage 2

• Unexplained moderate weight loss ( lt 10 body
  weight)
• Recurrent upper respiratory tract infection
• Herpes zoster
• Angular cheilitis
• Recurrent oral ulceration
• Papural pruritic eruption (PPE)
• Seborrheic dermatitis
• Fungal nail infection

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Stage 3

• The symptoms are mild The immune system
  deteriorates
• Emergence of opportunistic infections and cancers
  
• Unexplained severe weight loss (gt10 of body
  weight)
• Unexplained chronic diarrhea gt 1 month

• Unexplained persistence fever (temperature gt 37.5
  0C for 1 month)
• Persistence oral candidiasis
• Oral hair leukoplakia
• Pulmonary tuberculosis
• Acute necrotizing ulcerative stomatitis,
  gingivitis or periodontitis
• Unexplained anemia

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Stage 4 - HIV / AIDS

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• The immune system weakens
• The illnesses become more severe leading to an
  AIDS diagnosis

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Stage 4..

• Candidiasis of esophagus, trachea and bronchi
• Invasive cervical cancer
• Extra pulmonary cryptococcosis
• Chronic cryptosporidiosis gt 1 month
• Cytomegalovirus disease outside liver, spleen and
  nodes
• Herpes simplex
• HIV encephalopathy
• HIV wasting syndrome

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Stage 4..

• Chronic isosporodiasis gt 1 month
• Kaposi sarcoma
• Lymphoma
• Mycosis
• Pneumocystis carinii pneumonia (PCP)
• Progressive multifocal leucoencephalopathy
• Toxoplasmosis
• HIV associated neuropathy
• Symptomatic HIV associated cardiomyopathy
• Atypical disseminated leishmaniasis

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Opportunistic Infections

• People with healthy immune systems can be exposed
  to certain microbes and have no reaction to them.

• Opportunistic infections (OIs) are infections
  that occur more frequently and are more severe in
  individuals with weakened immune systems,
  including people with HIV.

These infections are called opportunistic
because they take advantage of your weakened
immune system, and they can cause devastating
illnesses.
But people living with HIV can face serious
threats from the same microbes.
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REFERENCES

• Brian R, Walker N, Stuart H. Davdsons Principle
  and Practice of Medicine 23rd Edition. HIV
  Infection and AIDS , Pg 323-337.
• Kasper F,hauser Longo. Harrisons Principles Of
  Internal Medicine 19th Edition. Human
  Immunodeficiency Virus Disease AIDS and Related
  Disorders pg 1215-1283.

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• THANKS