HIV and TB

Infection:

  • Invasion of the body by a pathogen & resulting signs & symptoms that develop in response to the invasion
  • Localized or systemic
  • Most common causes: bacteria, viruses, fungi, protozoa

Bacteria:

  • One-celled micro-organisms
  • Many considered normal flora
  • Cause disease when they enter body & grow inside cells (ex. TB) and/or secrete toxins that damage cells (ex. tetanus)

Viruses:

  • Not cells like bacteria
  • Consist of RNA or DNA & a protein envelope
    Can only reproduce in the cells of a living organism e.g. HIV

Antibiotic-Resistant Organisms (AROs) or Multi-Drug Resistant Organisms (MDROs):

  • Resistance: Occurs when pathological organisms change in ways that decrease the ability of a drug to treat disease
    Methicillin-resistant Staphylococcus aureus (MRSA)
    Vancomycin-resistant enterococci (VRE)
    Penicillin-resistant Streptococcus pneumoniae

Healthcare-Associated Infections:

  • Infections acquired in healthcare settings
  • estimated 8000 Canadians die in hospitals each year due to HAIs
  • At least 30% of HAIs can be prevented by following infection prevention strategies

Infection Precautions:

  • Guidelines issued by the CDC & Health Canada
  • Purpose: To prevent transmission of organisms between clients and healthcare providers

Routine Practices/Standard Practices:

  • for care of ALL clients in hospitals and health care settings regardless of diagnosis or presumed infection status

Additional Precautions:

  • for clients suspected of being infected with epidemiologically important pathogens that can be transmitted by:
  • air: need private room with negative flow; wear N95 mask (ex. measles, TB, varicella)
  • droplet: private or semi-private room; mask for activities within 1 metre of patient; ex. influenza, meningitis
  • contact (with dry skin or contaminated surfaces)

HIV

Canada:

  • Approximately 30% of persons living with HIV are not aware they are infected (PHAC, 2010)
  • number of new cases of HIV infection are not decreasing
    Most cases in men who have sex with men (MSM)
  • Heterosexual transmission becoming more prevalent, now most common method of infection for women
  • remains a disease of marginalized individuals

Transmission:

  • Only by contact with infected body fluids:
    blood, semen, vaginal secretions, breast milk
  • Not transmitted through: tears, saliva, urine, emesis, sputum, feces, sweat
  • Sexual intercourse with infected partner
  • Exposure to HIV-infected blood/blood products (sharing injection equipment; blood transfusions; workplace needle-stick)
  • Perinatal transmission during pregnancy at time of delivery or through breast feeding

Transmitting HIV during Pregnancy or Birth:

  • About 1/4 to 1/3 of untreated HIV-infected pregnant women will pass the infection to their babies
  • In general, pregnant women with HIV can use the same HIV regimens recommended for non-pregnant and should start as soon as possible
  • With treatment, & delivery by cesarean section, the chances of the baby being infected can be reduced to a rate of 1 percent
  • HIV can also spread to babies through breast milk of mothers infected with the virus
  • HIV- infected pregnant women (treated with zidovudine (ZDV=AZT=Retrovir) the rate of perinatal transmission is decreased; combination ART – decreased risk of perinatal transmission <2%)

Contact with Blood and Blood Products:

  • Exposes health care workers to:
    Acquired human immunodeficiency virus (HIV)
    Hepatitis A virus (rare)
    Hepatitis B virus (30%)
    Hepatitis C virus (3%)
  • Risk of HIV infection after a needle-stick exposure to HIV blood is 0.3% - 0.4%

Prevention:

  • Education & behavior change are most effective prevention tools
  • Educational messages should be specific to patient’s needs, culturally sensitive, language appropriate & age specific
  • Safe activities (those that eliminate risk)
  • Risk-reducing activities (those that decrease risk, but do not eliminate it)

Needle Stick Injuries:

  • Report all blood exposures


  • Routine post-exposure management includes serological markers of HIV, HBV & HCV infection


  • Post-exposure prophylaxis with combination ART based on type & volume of exposure, & the status of the source patient has been shown to significantly reduce the risk of infection


Routine Practices or Standard Precautions:

  • Hand hygiene: pre/post contact
  • Gloves: touching body fluids, secretions & contaminated items, mucous membranes & nonintact skin
  • Mask, eye protection/face shield: procedures likely to generate splashes or sprays of body fluids; within 1 m of coughing patient
  • Gown: procedures likely to generate splashes or sprays of body fluids

HIV: a ribonucleic acid (RNA) virus; retrovirus because it replicates in a "backward" manner going from RNA to deoxyribonucleic acid (DNA); can only replicate inside a living cell

Viral Load:

  • Initial infection
    • Viremia (large viral levels in blood) for 2 to 3 weeks (transmission is more likely when viral load is high)
    • Followed by prolonged period (years) of low viral load

Pathophysiology:

  • Cells with CD4 receptor sites are infected
    • CD4+ T cells (T helper cells)
    • Lymphocytes
    • Monocytes/macrophages
    • Astrocytes
    • Oligodendrocytes

  • HIV attacks these cells and uses them to make more copies of HIV


  • Weakens immune system, makes it unable to protect body from illness and infection


  • Immune dysfunction results mostly from destruction of CD4+ T cells (key cells for immune recognition and defense against pathogens)

  • Normal T cell life span is 100 days, whereas infected cells live only 2 days


  • Viral activity destroys 1 billion T cells daily


  • Adults normally have 800-1200 CD4+ T cells per microliter (µL) of blood


  • Immune problems start when CD4+ T cell counts drop below 500 cells/µL


Timeline:

  • Acute Retroviral Syndrome: first few weeks after HIV infection; before antibody test results become positive; characterized by fever, malaise, lymphadenopathy & skin rash; symptoms may be mistaken for a cold or flu
  • Early Chronic HIV Infection: 3 weeks to 3 months post infection; HIV antibody test becomes positive; CD4+ T cell count remains above 500 cells/µL; generally asymptomatic; flu-like symptoms often occur: fatigue, low-grade fever, night sweats, generalized lymphadenopathy; public health problem – individuals unaware they are infected
  • Intermediate Chronic Infection: viral load increases; CD4+ T lymphocyte count DROPS to 200 to 500 cells/µL; most common infection is oropharyngeal candidiasis or thrush; severe fatigue & night sweats
  • Late Chronic Infection or Acquired Immunodeficiency Syndrome (AIDS): immune system severely compromised
    CD4+ T cell count plummets; viral load surges; AIDS is diagnosed when an individual with HIV develops at least one of these conditions (CD4+ T cell count drops below 200 cells/ul; development of one of a list of opportunistic infections; development of one of a list of opportunistic cancers; wasting syndrome occurs; dementia develops)



Disease Progression Varies:

  • in untreated patients, the time between infection with HIV and the development of AIDS ranges from a few months to as long as 17 years (median: 10 years)
  • majority of individuals infected with HIV remain symptom-free for extended periods, but viral replication is active during all stages of infection and increases substantially as the immune system deteriorates

Testing and Counselling:

  • Pre & post-test counseling
  • Decreasing future risk of exposure
  • Protecting partners
  • Delay between infection & accurate test
  • Possibility of false-negative tests during window period
  • Positive test shows HIV infection & not AIDS
  • in many provinces, if test done through doctor’s office or clinic, results reported to health officials

Antibody Testing:

  • Sensitive screening test: enzyme immunoassay [EIA]
  • Reactive screening test: Rapid test – diagnosis of HIV-1 infection within 30 min
  • Reactive screening tests must be confirmed by a supplemental test (e.g., the Western blot [WB] or an immunofluorescence assay [IFA]
  • HIV antibody is detectable in at least 95% of patients within 3 months after infection
  • All infants born to HIV infected mothers will be positive on the HIV antibody test because maternal antibodies cross the placental barrier – these antibodies remain present in the infant up to 18 months
  • Need to test for HIV antigen – can definitively diagnose HIV in infected infants by 4 wks of age

Collaborative Care Focus:

  • Monitoring HIV disease progression and immune function
  • Initiating and monitoring antiretroviral therapy (ART)
  • Preventing and detecting opportunistic infections
  • Managing symptoms
  • Preventing and treating complications of therapies

Antiretroviral Therapy (ART):

  • Antiretroviral drugs work at various points in HIV replication cycle
  • HIV can become resistant to any of these drugs
  • When multiple drugs (three or more) are used in combination, it is referred to as antiretroviral drug therapy (ART)
  • Multidrug-therapy protocols have been shown to significantly reduce viral loads & reverse clinical progression of HIV

Drug Therapy:

  • Goals: decrease HIV RNA levels to less than 50 copies/uL; maintain or raise CD4+ T cell counts to greater than 200 cells/uL [a range of 800 to 1200 cells/uL is preferred]; delay development of HIV-related symptoms; treatment decisions should be individualized

  • Categories:


    • Protease inhibitors (PIs) (e.g. Invirase); interfere with activity of enzyme protease, inhibit viral replication at later step

    • Integrase inhibitors (e.g. Raltegravir); work by interfering with the enzyme integrase


    • Fusion (entry) inhibitors (e.g. Fuzeon); Interfere with HIV CD4 receptor site binding and entry into cells

    • Reverse Transcriptase Inhibitors (RTIs) nukes (nucleoside) or non-nukes (non-nuceloside); inhibit ability of HIV to make a DNA copy early in replication
  • Adherence: taking drugs as ordered; difference with HIV (missing a dose can lead to viral mutations that allow HIV to become resistant to drug), adherence rates > 95% are required to prevent disease progression


Drug Therapy for Opportunistic Diseases: HIV management is complicated by opportunistic disease that can develop due to a poor immune system

Pneumocytis carinii pneumonia (PCP): caused by fungus; can be prevented by antibiotics; clinical manifestations: non-productive cough, hypoxemia, progressive shortness of breath, fever, night sweats, fatigue

Cryptococcal meningitis: brain infections caused by fungus (found mainly in dirt and bird droppings)

Cytomegalovirus retinitis (CMV): infection of retina, occurs primarily in AIDS patients; clinical manifestations: lesions on retina, blurred vision, loss of vision

Mycobacterium avium complex (MAC): gastrointestinal system affected; serious infection; clinical manifestations: watery diarrhea and weight loss

Kaposi's sarcoma (KS): cancer that develops in connective tissues such as cartilage, bone, fat; clinical manifestations: firm, flat, raised or nodular, hyper pigmented multi-centric lesion

Tuberculosis:

  • Infectious disease caused by a bacterial infection (mycobacterium tuberculosis)
  • Confused with cancer, bronchitis, pneumonia
  • Usually attacks the lungs but can affect any part of the body (larynx, kidneys, meninges, bones, adrenal glands, lymph nodes)
  • Only TB in the lungs or throat is infectious
  • major adverse drug effect: hepatitis (requires liver function test monitoring)

Resurgence of TB:

  • Dramatic decrease in 1940s & 1950s due to introduction of chemotherapeutic agents
  • Now ~ 1600 new cases reported in Canada/year
  • High rates of TB co-infection with HIV
  • Multi-drug resistant (MDR) strains of TB
  • Immigration
  • Crowding in prisons/shelters
  • Healthcare workers considered to be at high risk

Etiology:

  • Spread via airborne droplets when infected person coughs, speaks, sneezes
  • Not spread by hands or objects

  • Brief exposure rarely causes infection


  • Transmission requires close, frequent or prolonged exposure


TB Infection (Latent TB):

  • Exposed to the TB bacteria but immune system strong enough to contain it


  • Positive skin test


  • No TB symptoms


  • Not contagious


  • At risk for developing the disease in future


  • May be given medication to prevent disease from developing (Isoniazid 9 or 6 months OR Isoniazid and Rifapentine for 3 months OR Rifampin for 4 months)


TB Disease:

  • TB bacteria is actively replicating


  • TB skin test and sputum test may be positive


  • Most show active TB on x-ray/CT/MRI of chest or other body parts (lymph nodes, spine, kidneys)


  • Symptoms become worse over time


  • Contagious if in the lungs/throat and not treated


  • Needs treatment with several medications for months or longer to cure disease


Clinical Manifestations:

  • Cough > 3 weeks
  • Pleuritic pain
  • Abnormal chest x-ray
  • Fever and/or chills
  • Night sweats
  • Unexplained weight loss
  • Hemoptysis (coughing blood) not common
  • Dyspnea unusual

Medical Management:

  • Standard therapy revised due to increased prevalence of MDR TB
  • MDR TB occurs when resistance develops to two or more anti-TB drugs
  • Managed aggressively with a combination of at least 4 drugs (to increase therapeutic effectiveness; to decrease development of resistant strains)

TB Medications:

  • Five primary medications
    Isoniazid (INH)
    Rifampin (RMP)
    Pyrazinamide (PZA)
    Streptomycin
    Ethambutol (EMB)
  • Various drug & dosing combinations
  • Combination drugs may enhance adherence
    Rifamate: INH & RMP
    Rifater: INH, RMP & pyrazinamide
  • Patients on antiretroviral drugs for HIV cannot take RMP (interferes with ART)