Late presenters and opportunistic infections

Jane BrutonClinical Research NurseImperial 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/mm3or presenting with an AIDS-defining event, regardless of the CD4.

• 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)

Late diagnosis in Europe

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.

• 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?

• Stigma• Fear• Ignorance• Lack of availability of testing

How can we reduce late presentation?

• Increase HIV testing • Universal Opt out testing• Increasing HIV Knowledge• Reducing Stigma• What is feasible with limited resources?

Opportunistic infectionsCalled “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 infectionsCD4 > 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)• 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

• 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)

specialim m une cells form a barrier shell (in th isexam ple,bacilli arein the lungs)

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TB pathogenesisTB disease

• 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

shell breaks down and tuberclebacilli escape

m ultip ly(in th is exam ple,TB disease develops in the lungs)

and

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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

TB infectionand NO risk factors

TB infection and HIV infection

(pre-Highly Active Antiretroviral Treatment

[HAART])

Risk is about 5% in the first 2 years after infection and about 10% over a lifetime

Risk is about 7% to 10% PER YEAR, a very high risk over a lifetime

Progression to TB diseaseTB and HIV

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 TBMono-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)

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

Suggested timing for starting ARV’s in HIV/TB co-infection (BHIVA,EACS guidelines 2011)

Immune Reconstitution Inflammatory Syndrome (IRIS)

• IRIS = worsening or appearance of new signs, symptoms or radiological abnormalities, occurring after starting ARV’s

• Symptoms: – 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)• 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: • 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 infections100-200 cells/mm3 :• Pneumocystis Jirovecii (Carinii) Pneumonia(PCP)• Histoplasmosis and Coccidioidomycosis• Progressive Multifocal Leukoencephalopathy(PML)

Progressive Multifocal Leukoencephalopathy

• 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 infections50-100 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 birdsSymptoms• 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 dissemninatedSigns and Symptoms of MAC: •Fevers, night sweats, abdominal pain, fatigue, diarrhoeaTreatment•Antimycobactrial, (Azithromycin or clarithromycin and Ethambutol)

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)