Transcript Late presenters and opportunistic infections

Late presenters and
opportunistic infections
Jane Bruton
Clinical Research Nurse
Imperial College
Definitions
Late presentation:
Person presenting for care with a CD4
<350/mm3 cells
or presenting with an AIDS-defining event,
regardless of the CD4.
Definitions
Presentation with advanced HIV disease:
Person presenting for care with a CD4
<200/mm3
or presenting with an AIDS-defining event,
regardless of the CD4.
Late diagnosis in Europe
• In 2012 half of the cases of HIV were
reported as late presenters (LP) (CD4
<350/mm3)
• 30% of late presenters had advanced HIV
infection (CD4 <200/mm3)
Europe
• Rate of late presentation are declining in
MSM.
• People over 50 are more likely to present late
in infection.
• Immigrants more likely to be late presenters.
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Hofstra M et al. Late presentation of HIV infection in Europe. 14th European AIDS Conference,
Brussels, abstract LBPS8/3, 2013.
Romania late presenters
• 35% of new cases in 2013 were 20 – 24 and were late
presenters
• Heterosexuals high number of late presenters
• MSM early- proactive presenters
• IVDU early - through medical screening
• Many late presenters have co-morbidities (HCV, HBV,
TB and STI’s)
• High medical and psycho-social needs
Country Progress Report on AIDS
Romania Reporting period January 2013 – December 2013 2014
COHERE study
• Late presentation is associated with an
increased rate of AIDS/deaths, particularly in
the first year after HIV diagnosis.
• Late presentation or very late presentation
significantly increases the risk of AIDS/death
in the first two years after entry into HIV care
Mocroft A et al. Risk factors and outcomes for late presentation for HIV-positive persons in
Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe
Study (COHERE). PLOS Medicine: 10:9, e1001510, 2013.
Why do people present late?
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Stigma
Fear
Ignorance
Lack of availability of testing
How can we reduce late presentation?
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Increase HIV testing
Universal Opt out testing
Increasing HIV Knowledge
Reducing Stigma
What is feasible with limited resources?
Opportunistic infections
Called “opportunistic” because they take
advantage of the weakened immune system.
With healthy immune systems exposure to
certain viruses, bacteria, or parasites cause no
problems.
These same bacteria and viruses cause great
damage to a weakened immune system.
Opportunistic infections
CD4 > 500 cells/mm3
•usually not at risk
CD4 200-500 cells/mm3 :
•Candidiasis (Thrush)
•Kaposi’s Sarcoma (KS)
•Pulmonary Tuberculosis (PTB)
•Lung infections
Tuberculosis (TB)
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Mycobacterium tuberculosis
Can occur at any CD4
TB treated first if CD4 >350
Pulmonary or extrapulmonary
Risk of TB is 12-20 x greater in HIV+ve people
Tx with anti TB antibiotics for 6-9 months
Tuberculosis (TB)
Symptoms
• A cough that lasts for more than 2-3 weeks
• Coughing up phlegm or blood
• Chest pain
• Weakness or fatigue
• Weight loss
• Lack of appetite
• Fever or chills
• Night sweats
TB Pathogenesis
Latent Infection LTBI
4
special
immune cells
form a barrier
shell (in this
example,
bacilli are
in the lungs)
• Within 2 to 8 weeks the immune system produces special immune cells
called macrophages that surround the tubercle bacilli
• These cells form a barrier shell that keeps the bacilli contained and under
control (LTBI)
TB pathogenesis
TB disease
5
shell breaks
down and
tubercle
bacilli escape
and multiply
(in this example,
TB disease
develops in
the lungs)
• If the immune system CANNOT keep tubercle bacilli under control, bacilli
begin to multiply rapidly and cause TB disease
• This process can occur in different places in the body
Transmission
• Probability that TB will be transmitted depends on:
– Infectiousness of person with TB disease
– Environment in which exposure occurred
– Length of exposure
– Virulence (strength) of the tubercle bacilli
• The best way to stop transmission is to:
– Isolate infectious persons
– Provide effective treatment to infectious persons as soon as
possible
Progression to TB disease
TB and HIV
TB infection
and NO risk factors
Risk is about 5% in
the first 2 years after
infection and about
10% over a lifetime
TB infection
and HIV infection
(pre-Highly Active
Antiretroviral Treatment
[HAART])
Risk is about 7% to
10% PER YEAR, a
very high risk over a
lifetime
TB in HIV
• TB is more difficult to diagnose in PLWH
• TB progresses faster in PLWH
• TB is more likely to be fatal in PLWH if undiagnosed
or left untreated
• TB occurs earlier in HIV infection than other Ois
(once TB infection is acquired, HIV impairs the ability
to
contain new TB infection)
Signs and Symptoms
• Signs and symptoms comparable to non-HIV infected
individuals
However in advanced HIV infection….
• TB often presents atypically with extrapulmonary disease
• In extrapulmonary disease symptoms usually not
localized to particular organ or site
• CXR may reveal adenopathy, atypical infiltrates, pleural
effusions or miliary disease OR may reveal no
abnormality at all
Treatment
• 4 drugs - initial phase
• 2/12 initial phase - isoniazid, rifampicin, pyrazinamide
and ethambutol (if organism fully susceptible,
ethambutol may be stopped)
• Continuation phase - 4/12 (longer depending on
circumstances) isoniazid and rifampicin
• Pyridoxine (vitamin B6) for all patients with isoniazid
dosing
• Duration of TB treatment the same - HIV positive and
negative
Drug-Resistant TB
Mono-resistant
Resistant to any one TB treatment drug
Poly-resistant
Resistant to at least any 2 TB drugs (but not
both isoniazid and rifampin)
Multidrug resistant
(MDR TB)
Resistant to at least isoniazid and rifampin, the 2
best first-line TB treatment drugs
Extensively drug
resistant
(XDR TB)
Resistant to isoniazid and rifampin, PLUS
resistant to any fluoroquinolone AND at least 1
of the 3 injectable second-line drugs (e.g.,
amikacin, kanamycin, or capreomycin)
Suggested timing for starting ARV’s in HIV/TB
co-infection (BHIVA,EACS guidelines 2011)
CD4 count cells/µl
When to treat with ARTs
<100cells/µl
As soon as possible: after
starting TB therapy
100-350cells/µl
As soon as possible, but can
wait until after completion of 2
months of TB Rx
CD4 consistently
>350cells/µl
At the discretion of the treating
physician
Immune Reconstitution
Inflammatory Syndrome (IRIS)
• IRIS = worsening or appearance of new signs, symptoms or
radiological abnormalities, occurring after starting ARV’s
• Symptoms:
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Fever
Worsening infiltrates or effusion,
mediastinal & peripheral lymphadenopathy (enlarging & painful)
abscesses
intracranial tuberculomas
• Appears in the first 1-6 weeks of ARV Rx
• No diagnostic test
• Treat with high dose corticosteroids
Kaposi’s Sarcoma (KS)
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Human Herpes Virus-8
Purple lesions on the body, the mouth, and internal organs
Occasionally gastrointestinal complaints with disseminated KS
Treated with chemotherapy and ART
Candidiasis (Thrush)
Oral/ Oesophageal thrush symptoms include:
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White patches on gums, tongue, throat or lining of the mouth
Pain in the mouth, throat, or chest
Difficulty swallowing, loss of appetite
Nausea, vomiting, weight loss
Treated with antifungal medicine
• Topical agents
• Fluconazole PO or IV
• amphotericin B
Opportunistic infections
100-200 cells/mm3 :
• Pneumocystis Jirovecii (Carinii) Pneumonia
(PCP)
• Histoplasmosis and Coccidioidomycosis
• Progressive Multifocal Leukoencephalopathy
(PML)
Progressive Multifocal
Leukoencephalopathy
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Rare, usually fatal
Progressive damage to the white matter
Caused by JC virus
Weakness or paralysis
Vision loss, impaired speech, cognitive deterioration
Treatment
• ART
Pneumocystis Jirovecii Pneumonia
(PCP)
Signs and symptoms
• Shortness of breath, fever
• Dry cough, chest pain
Treatment (antifungal agents)
Prophylaxis with CD4<200
Opportunistic infections
50-100 cells/mm3 :
•Toxoplasmosis
•Cryptosporidiosis
•Cryptococcal Infection
•Cytomegalovirus (CMV)
<50 cells/mm3 :
•Mycobaterium Avium complex (MAC)
Cytomegalovirus (CMV)
• Common virus
• Can attack several parts of the body
• Commonly CMV retinitis (causes blindness)
Treatment with Ganciclovir
then ART (after initial CMV tx)
Toxoplasmosis
• Parasite Toxoplasma gondii
• Causes encephalitis and neurological disease
• The parasite is carried by cats and birds
Symptoms
• Headache, confusion, motor weakness, fever
and seizures
• Treatment with anti protozoal (pyrimethamine)
and antibiotics (sulphadiazine)
Mycobaterium Avium complex
(MAC)
•Bacteria that can be found in soil or water
•Infects, lungs, intestines or dissemninated
Signs and Symptoms of MAC:
•Fevers, night sweats, abdominal pain, fatigue,
diarrhoea
Treatment
•Antimycobactrial, (Azithromycin or clarithromycin
and Ethambutol)
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AIDS defining
Pneumocystis jirovecii pneumonia
Recurrent severe bacterial pneumonia
Chronic herpes simplex infection
Candidiasis: Esophageal, bronchi, trachea or lungs
Extra pulmonary, pulmonary, disseminated tuberculosis
Kaposi’s sarcoma
Cytomegalovirus, disease and retinitis
Encephalopathy, HIV related
Herpes simplex, bronchitis, pneumonitis, esophagitis, chronic>1mth
Disseminated mycosis (extrapulmonary histoplasmosis, coccidiomycosis)
Mycobacterium (avium complex, TB, kansasii, other)
Progressive multifocal leukoencephalopathy
Chronic cryptosporidiosis
Chronic isosporiasis
Lymphoma (cerebral, Burkitt’s, immunoblastic,non-Hodgkin)
Salmonella (sepsis, recurrent)
Toxoplasmosis (brain)
Wasting syndrome
Pneumonia (recurrent)
Cervical cancer (invasive)