Late presenters and - PowerPoint Presentation

Slide1

Late presenters and opportunistic infections

Jane

Bruton

Clinical Research Nurse

Imperial CollegeSlide2

DefinitionsLate presentation: Person presenting for care with a CD4 <350/mm3 cells

or

presenting with an AIDS-defining event, regardless of the

CD4. Slide3

DefinitionsPresentation with advanced HIV disease: Person presenting for care with a CD4

<200/mm3

or

presenting with an AIDS-defining event, regardless of the

CD4.Slide4

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 EuropeSlide5

EuropeRate 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.   Slide6

Romania late presenters35% of new cases in 2013 were 20 – 24 and were late presentersHeterosexuals high number of late presentersMSM early- proactive presentersIVDU early - through medical screeningMany late presenters have co-morbidities (HCV, HBV, TB and STI’s)High medical and psycho-social needsCountry Progress Report on AIDS Romania Reporting period January 2013 – December 2013 2014Slide7

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. Slide8

Why do people present late?StigmaFearIgnorance

Lack of availability of testingSlide9

How can we reduce late presentation?

Increase HIV testing

Universal Opt out testing

Increasing HIV Knowledge

Reducing Stigma

What is feasible with limited resources?Slide10
Slide11

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.Slide12

Opportunistic infectionsCD4 > 500 cells/mm3 usually not at risk

CD4 200-500 cells/mm

3

:

Candidiasis (Thrush)

Kaposi’s Sarcoma (KS)

Pulmonary Tuberculosis (PTB

)

Lung infectionsSlide13

Tuberculosis (TB)Mycobacterium tuberculosis Can occur at any CD4TB 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 monthsSlide14

Tuberculosis (TB)SymptomsA 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 sweatsSlide15

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)Slide16

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 bodySlide17

TransmissionProbability that TB will be transmitted depends on:Infectiousness of person with TB diseaseEnvironment in which exposure occurredLength of exposureVirulence (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 possibleSlide18

TB infection

and 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 disease

TB and HIVSlide19

TB in HIVTB is more difficult to diagnose in PLWHTB progresses faster in PLWHTB 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)Slide20

Signs and SymptomsSigns and symptoms comparable to non-HIV infected individualsHowever 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 allSlide21

Treatment4 drugs - initial phase2/12 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 negativeSlide22

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)Slide23

CD4 count cells/µl

When to treat with ARTs

<100

cells/

µl

As soon as possible: after starting TB therapy

100-350

cells/

µl

As soon as possible, but can wait until after completion of 2 months of TB Rx

CD4 consistently

>350

cells/

µl

At the discretion of the treating physician

Suggested timing for starting ARV’s in HIV/TB co-infection (BHIVA,EACS guidelines 2011) Slide24

Immune Reconstitution Inflammatory Syndrome (IRIS)IRIS = worsening or appearance of new signs, symptoms or radiological abnormalities, occurring after starting ARV’s Symptoms: FeverWorsening 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 corticosteroidsSlide25

Kaposi’s Sarcoma (KS)Human Herpes Virus-8Purple lesions

on the

body, the mouth, and internal organs

Occasionally gastrointestinal complaints with disseminated

KS

Treated with chemotherapy and ARTSlide26

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 s

wallowing, loss

of

appetite

Nausea, vomiting, weight loss

Treated with antifungal medicine

Topical agents

Fluconazole PO or IV

amphotericin BSlide27

Opportunistic infections100-200 cells/mm3 :Pneumocystis Jirovecii

(

Carinii

) Pneumonia

(PCP)

Histoplasmosis

and

Coccidioidomycosis

Progressive Multifocal

Leukoencephalopathy

(PML)Slide28

Progressive Multifocal LeukoencephalopathyRare, usually fatalProgressive damage to the white matterCaused by JC virus

Weakness or paralysis

Vision loss, impaired speech, cognitive deterioration

Treatment

ARTSlide29

Pneumocystis Jirovecii Pneumonia (PCP)Signs and symptomsShortness of breath, feverDry

cough, chest pain

Treatment (antifungal agents)

Prophylaxis with CD4<200Slide30

Opportunistic infections50-100 cells/mm3 :Toxoplasmosis

Cryptosporidiosis

Cryptococcal Infection

Cytomegalovirus (CMV)

<50 cells/mm

3

:

Mycobaterium Avium complex (MAC)Slide31

Cytomegalovirus (CMV)Common virusCan attack several parts of the bodyCommonly CMV retinitis (causes blindness)

Treatment with

Ganciclovir

then ART (after initial CMV

tx

)Slide32

ToxoplasmosisParasite 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

)Slide33

Mycobaterium Avium complex (MAC) Bacteria that can be found in soil or waterInfects, lungs, intestines or dissemninated

Signs and Symptoms of MAC:

Fevers, night sweats, abdominal pain, fatigue, diarrhoea

Treatment

Antimycobactrial, (Azithromycin or clarithromycin and Ethambutol) Slide34

AIDS defining Pneumocystis jirovecii pneumoniaRecurrent 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)Slide35