2003/041 clinical hiv infection gail crowe princess alexandra hospital

2003/042003/04 11

Clinical HIV infectionClinical HIV infection

Gail CroweGail Crowe

Princess Alexandra HospitalPrincess Alexandra Hospital

2003/042003/04 22

ObjectivesObjectives

EpidemiologyEpidemiology Natural historyNatural history SeroconversionSeroconversion Testing for HIVTesting for HIV HIV indicator diseasesHIV indicator diseases TreatmentTreatment

2003/042003/04 44

Global Estimates for Adults Global Estimates for Adults and Children 2007and Children 2007

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Estimated Number of People Estimated Number of People Living With HIV Globally Living With HIV Globally

1990-20071990-2007

2003/042003/04 66

Estimated Number of Adult and Estimated Number of Adult and Child Deaths Due to HIV Globally Child Deaths Due to HIV Globally

1990-20071990-2007

2003/042003/04 77

Adults and Children Living Adults and Children Living With HIV Globally 2007With HIV Globally 2007

2003/042003/04 88

Estimated number of adults (15-59 years) living with HIV (both diagnosed and undiagnosed) in the UK: 2008

6,550

4,5505,450

1,200550450 150

13,850

24,350

2,1502,250

4,0502,850

8,950

0

5,000

10,000

15,000

20,000

25,000

MSM Heterosexualmen born in

Africa

Heterosexualwomen born in

Africa

Heterosexualmen born in

UK/elsewhere

Heterosexualwomen born inUK/elsewhere

Injecting druguser men

Injecting druguser women

Es

tim

ate

d n

um

be

r o

f p

eo

ple

liv

ing

HIV

Diagnosed

Undiagnosed

Total = 77,550 (73,000 - 83,300)Excludes 5,450 HIV infections among individuals outside the 15-59 years age range

MESH Department - Centre for Infections

2003/042003/04 99

Diagnosed HIV-infected persons accessing Diagnosed HIV-infected persons accessing care by prevention groupcare by prevention group11 and ethnic and ethnic

groupgroup22, UK, UK

Annual survey of HIV-infected persons accessing care

1Numbers accessing care exclude those where exposure category was not reported (1,552 in 2006)2Ethnic group was allocated proportionally where it was not reported

1997 1998 1999

0

5,000

10,000

15,000

20,000

2000 2001 2002 2003 2004 2005 2006

Nu

mb

ers

ac

ce

ss

ing

ca

re

White MSM

Black African heterosexuals

Non-white MSM

All other heterosexuals

IDU

Other

White heterosexuals

2003/042003/04 1010

UK number of HIV diagnoses by UK number of HIV diagnoses by year of diagnosisyear of diagnosis

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2003/042003/04 1111

Number of new HIV diagnoses¹ by prevention group², UK: 1999-2008

0

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Ne

w H

IV d

iag

no

ses

MSM

Heterosexual contact in the UK

Heterosexual contact abroad

IDU

Blood product recipients

Mother-to-child transmission

¹ Numbers will rise as further reports are received, particularly for recent years² Adjustments made for missing information relating to patient exposure


2003/042003/04 1212

Estimated late diagnosis of HIV infection by prevention group among adults aged ≥15 years, UK: 2008

Number diagnosed = 2,760 1,630 2,950 170 7,218

20%

44%

36%

30% 32%

43%

65%61%

52%55%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

MSM Heterosexual men Heterosexual women Injecting drug users Overall

Pe

rce

nta

ge

dia

gn

os

ed

late

<200

<350

CD4 cell counts <200 cells/mm³ within three months of diagnosis


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HIV in the UK: 2008HIV in the UK: 2008

83,000 living with HIV83,000 living with HIV 22,400 unaware of diagnosis22,400 unaware of diagnosis

40% of HIV probably acquired in UK40% of HIV probably acquired in UK 2/3 of these are in gay men2/3 of these are in gay men

31% of new diagnoses “late”31% of new diagnoses “late” ie CD4 <200ie CD4 <200

56,556 HIV+ people accessed care56,556 HIV+ people accessed care 70% on ARVs70% on ARVs 8% >55 yrs old8% >55 yrs old

2003/042003/04 1515

HIV Attendances at PAHHIV Attendances at PAH

0

20

40

60

80

100

120

140

160

1997 1999 2001 2003 2005 2007 2009

3-D Column 1

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HIV Attendances by Risk HIV Attendances by Risk FactorFactor

010

2030

4050

6070

8090

100

1997 1999 2001 2003 2005 2007 2009

Gay menBlack AfricanIVDUWhite HeterosexualOther

2003/042003/04 1717

Attendances by CDC GradeAttendances by CDC Grade

0

20

40

60

80

100

120

1997 1999 2001 2003 2005 2007 2009

ABC

2003/042003/04 1818

Natural historyNatural history

Over course of infection: Over course of infection: CD4 count declines & HIV viral load increasesCD4 count declines & HIV viral load increases Increasing risk of developing infections and Increasing risk of developing infections and

tumourstumours The severity of these illnesses is greater the The severity of these illnesses is greater the

lower the CD4 count lower the CD4 count Most AIDS diagnoses occur at CD4 count <200Most AIDS diagnoses occur at CD4 count <200

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Acute infection – seroconversion

Asymptomatic

HIV related illnesses

AIDS defining illness

Death

2003/042003/04 2020

Primary HIV / seroconversionPrimary HIV / seroconversion

Approximately 30 - 60% of patients Approximately 30 - 60% of patients have a seroconversion illness. have a seroconversion illness.

Abrupt onset 2 – 4 weeks post Abrupt onset 2 – 4 weeks post exposure, self limiting 1 – 2 weeks exposure, self limiting 1 – 2 weeks

Symptoms generally non-specific and Symptoms generally non-specific and differential diagnosis includes range of differential diagnosis includes range of common conditionscommon conditions

Serological tests for HIV antibodies Serological tests for HIV antibodies may be negative or show may be negative or show indeterminate responseindeterminate response

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Symptoms include:Symptoms include:

Flu-like illness Flu-like illness FeverFever Malaise and lethargy Malaise and lethargy PharyngitisPharyngitis Lymphadenopathy Lymphadenopathy Toxic exanthemaToxic exanthema Occasionally HIV / AIDS defining illness due Occasionally HIV / AIDS defining illness due

to profound damage to immune system to profound damage to immune system (often temporary) e.g. oro-pharyngeal (often temporary) e.g. oro-pharyngeal candida, zoster, PCPcandida, zoster, PCP

2003/042003/04 2222


Acute infection – seroconversion

Asymptomatic

HIV related illnesses

AIDS defining illness

Death

2003/042003/04 2323

HIV associated conditionsHIV associated conditions

Most of these conditions are common in Most of these conditions are common in the general population. the general population.

Think of HIV if presentation is: Think of HIV if presentation is: atypical atypical recurrent problem recurrent problem severe severe

Suspicion may be increased if the Suspicion may be increased if the individual is at possible risk of HIV individual is at possible risk of HIV

infectioninfection

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Healing herpes zoster

Picture from St George’s Hospital for educational use only

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Oral Candida


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Severe oral hairy leukoplakia


2003/042003/04 2727

0 TimeHI V RNA HI V ab CD4

Opportunistic

Infections

Symptomatic HIV Infection

Symptoms and parameters over time

2003/042003/04 2828

Treatment for HIVTreatment for HIV

MonotherapyMonotherapy Dual therapyDual therapy Triple / quadruple therapyTriple / quadruple therapy

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Treatment for HIV (2)Treatment for HIV (2)

Nucleoside / nucleotide reverse Nucleoside / nucleotide reverse transcriptase inhibitors (Nucs)transcriptase inhibitors (Nucs)

Non nucleoside reverse transcriptase Non nucleoside reverse transcriptase inhibitors (NNRTI)inhibitors (NNRTI)

Protease inhibitors (PI)Protease inhibitors (PI) Fusion inhibitorsFusion inhibitors Integrase inhibitorsIntegrase inhibitors CCR5 inhibitorsCCR5 inhibitors

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Treatment for HIV (3)Treatment for HIV (3)

Nucs: AZT, 3TC, , Abacavir, DDI, D4T, FTC, Nucs: AZT, 3TC, , Abacavir, DDI, D4T, FTC, TenofovirTenofovir

NNRTIs: Efavirenz, Nevirapine, Etravirine NNRTIs: Efavirenz, Nevirapine, Etravirine PIs: Lopinavir, Atazanavir, Darunavir, PIs: Lopinavir, Atazanavir, Darunavir,

Amprenavir, Saquinavir, Indinavir, RitonavirAmprenavir, Saquinavir, Indinavir, Ritonavir Fusion Inhibitors: T20Fusion Inhibitors: T20 Integrase Inhibitors: RaltegravirIntegrase Inhibitors: Raltegravir CCR5 Inhibitors: MaravirocCCR5 Inhibitors: Maraviroc

2003/042003/04 3131

Side Effects of TreatmentSide Effects of Treatment

Nausea and vomiting, diarrhoeaNausea and vomiting, diarrhoea Anaemia / pancytopaenia / abn LFTsAnaemia / pancytopaenia / abn LFTs InsomniaInsomnia RashRash LipodystrophyLipodystrophy Pancreatitis, peripheral neuropathy, Pancreatitis, peripheral neuropathy,

lactic acidosis, renal stoneslactic acidosis, renal stones

2003/042003/04 3232

Monitoring TreatmentMonitoring Treatment

See 3 monthlySee 3 monthly Viral loadViral load CD4 countCD4 count Resistance testsResistance tests Therapeutic drug monitoringTherapeutic drug monitoring

2003/042003/04 3333

BHIVA GuidelinesBHIVA Guidelines

Launched September 2008Launched September 2008 Suggest HIV testing should be Suggest HIV testing should be

offered and recommended inoffered and recommended in Gay menGay men Intravenous drug usersIntravenous drug users People from high prevalence areas (sub People from high prevalence areas (sub

Saharan Africa)Saharan Africa) Sexual partners of the aboveSexual partners of the above

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Risk AssessmentRisk Assessment

Gay men – LondonGay men – London Gay men – outside Gay men – outside

LondonLondon IVDU – LondonIVDU – London IVDU – not LondonIVDU – not London Sub-Saharan AfricaSub-Saharan Africa

19.1%19.1% 4.3%4.3%

3.5%(M)3.5%(M) 5.0%(F) 5.0%(F) 0.77%(M) 0.34%(F)0.77%(M) 0.34%(F) 5.8%(M) 8.9% (F)5.8%(M) 8.9% (F)

2003/042003/04 3535


Also suggest universal testing inAlso suggest universal testing in GUM clinicsGUM clinics Antenatal servicesAntenatal services TOP servicesTOP services Drug dependency unitsDrug dependency units TB unitsTB units Patients with Hepatitis BPatients with Hepatitis B Patients with Hepatitis CPatients with Hepatitis C Patients with lymphomaPatients with lymphoma

2003/042003/04 3636


Also suggest universal testing inAlso suggest universal testing in GUM clinicsGUM clinics ✔✔ Antenatal servicesAntenatal services ✔✔ TOP servicesTOP services ✔✔ Drug dependency unitsDrug dependency units ✔✔ TB unitsTB units ✔✔ Patients with Hepatitis BPatients with Hepatitis B ✘✘ Patients with Hepatitis CPatients with Hepatitis C ✘✘ Patients with lymphomaPatients with lymphoma ✘✘

2003/042003/04 3737


Suggest that where an HIV indicator Suggest that where an HIV indicator disease is present, then testing disease is present, then testing should be offeredshould be offered

2003/042003/04 3838

Clinical Indicator Disease for Clinical Indicator Disease for HIVHIV

TBTB PCPPCP ToxoToxo Cerebral lymphomaCerebral lymphoma Crypto meningitisCrypto meningitis PMLPML

Bacterial Bacterial pneumoniapneumonia

AspergillosisAspergillosis Aseptic meningitisAseptic meningitis EncephalitisEncephalitis SOLSOL Cerebral abscessCerebral abscess Guillain BarreGuillain Barre DementiaDementia Peripheral Peripheral

neuropathyneuropathy Transverse myelitisTransverse myelitis

2003/042003/04 3939


KSKS CryptospoidiosisCryptospoidiosis

Seb dermatitisSeb dermatitis Severe psoriasisSevere psoriasis Severe shinglesSevere shingles Oral candidaOral candida OHLOHL Persistent diarrhoeaPersistent diarrhoea Shigella, Shigella,

Campylobacter, Campylobacter, SalmonellaSalmonella

Unexplained wt lossUnexplained wt loss Hep B, Hep CHep B, Hep C

2003/042003/04 4040

Kaposi’s sarcoma


2003/042003/04 4141


KSKS CryptospoidiosisCryptospoidiosis

Seb dermatitisSeb dermatitis Severe psoriasisSevere psoriasis Severe shinglesSevere shingles Oral candidaOral candida OHLOHL Persistent diarrhoeaPersistent diarrhoea Shigella, Shigella,

Campylobacter, Campylobacter, SalmonellaSalmonella

Unexplained wt lossUnexplained wt loss Hep B, Hep CHep B, Hep C

2003/042003/04 4242


NHLNHL Cervical cancerCervical cancer

Hodgkins lymphomaHodgkins lymphoma Lung caLung ca Anal cancer / AINAnal cancer / AIN Head and neck Head and neck

cancerscancers SeminomaSeminoma Castlemans diseaseCastlemans disease VINVIN CIN 2 or aboveCIN 2 or above Thrombocytopenia, Thrombocytopenia,

neutropenia, neutropenia, lymphopenialymphopenia

2003/042003/04 4343


CMV retinitisCMV retinitis Infective retinal Infective retinal disease or disease or unexplained unexplained retinopathyretinopathy

Unexplained Unexplained lyphadenopathylyphadenopathy

Chronic parotitisChronic parotitis ““Glandular fever”Glandular fever” PUOPUO Any STIAny STI

2003/042003/04 4444

BHIVA Guidelines on HIV BHIVA Guidelines on HIV TestingTesting

Suggest that, where prevalence of Suggest that, where prevalence of HIV exceeds 2/1000 consideration HIV exceeds 2/1000 consideration should be given to testingshould be given to testing all medical admissions all medical admissions all patients registering with a GPall patients registering with a GP

2003/042003/04 4545

HIV Prevalence By PCTHIV Prevalence By PCTPCTPCT Number Number

accessing accessing HIV careHIV care

Population Population in 1000sin 1000s

HIV HIV prevalence prevalence per 1000per 1000

LambethLambeth 2,3392,339 196.2196.2 11.911.9

Tower Tower HamletsHamlets

836836 152152 5.55.5

SouthendSouthend 259259 93.893.8 2.762.76

HarlowHarlow 101101 4848 2.12.1

2003/042003/04 4646

HIV – pre test discussionHIV – pre test discussion Informed consentInformed consent Advantages and disadvantagesAdvantages and disadvantages Risk assessmentRisk assessment 3 month window period3 month window period Preparing for the resultPreparing for the result Getting the resultGetting the result Health promotionHealth promotion

2003/042003/04 4747

Raising the subject of an HIV Raising the subject of an HIV testtest

Communication strategiesCommunication strategies

Raising the subject of HIV with a patient can Raising the subject of HIV with a patient can be difficult. be difficult.

‘ ‘The problems that you have had recently The problems that you have had recently are quite common, and usually minor. are quite common, and usually minor. However, very occasionally they can give a However, very occasionally they can give a clue that your immune system is not clue that your immune system is not working as well as it should.’ ‘I don’t know if working as well as it should.’ ‘I don’t know if you are at risk of HIV, but this is one you are at risk of HIV, but this is one condition that can affect the immune condition that can affect the immune system. Could I ask you some questions to system. Could I ask you some questions to see if you could be at risk?’ .see if you could be at risk?’ .

2003/042003/04 4848


Communication strategiesCommunication strategies • • Raise the subject of HIV before a Raise the subject of HIV before a

sexual history has been taken – sexual history has been taken – perhaps in a contraception or smear perhaps in a contraception or smear consultation. ‘HIV is much more consultation. ‘HIV is much more common in people from Africa. Do you common in people from Africa. Do you know people who have been affected? know people who have been affected? Would you like to consider having a Would you like to consider having a test?’test?’

• • Raise the subject of sexual health in Raise the subject of sexual health in a new patient check. ‘We find that a new patient check. ‘We find that quite a lot of young men are at risk of quite a lot of young men are at risk of having sexual health problems. Could I having sexual health problems. Could I ask you a few questions to see if you ask you a few questions to see if you are at risk?’are at risk?’

2003/042003/04 4949


Communication strategiesCommunication strategies

• • Raise the subject of HIV once a sexual history Raise the subject of HIV once a sexual history has been taken. ‘Because two of your partners has been taken. ‘Because two of your partners in the last year have been male, like you, it is in the last year have been male, like you, it is possible that you are at higher risk of HIV. possible that you are at higher risk of HIV. Have you ever considered having an HIV test?’Have you ever considered having an HIV test?’

• • Raise the subject of HIV when a history of Raise the subject of HIV when a history of injecting drug use has been identified. ‘Current injecting drug use has been identified. ‘Current advice is that everyone who has injected drugs advice is that everyone who has injected drugs in the past should be offered a test for HIV. in the past should be offered a test for HIV. Have you ever considered having a test?’Have you ever considered having a test?’

• • Remember to emphasise the benefits of Remember to emphasise the benefits of earlier HIV diagnosis.earlier HIV diagnosis.

2003/042003/04 5050

Risk AssementRisk Assement

Sexual behaviour and that of partnersSexual behaviour and that of partners Nationality, country of exposureNationality, country of exposure History of IVDUHistory of IVDU Rape/sexual assaultRape/sexual assault Occupational exposureOccupational exposure Invasive procedures in unsterile conditionsInvasive procedures in unsterile conditions Blood/blood products / organ recipient 1975-1985 Blood/blood products / organ recipient 1975-1985

(UK)(UK)

2003/042003/04 5151

Medical benefits of early HIV Medical benefits of early HIV diagnosisdiagnosis

Treatments available (HAART) not cure, Treatments available (HAART) not cure, but prevent people becoming unwellbut prevent people becoming unwell

Prophylaxis against opportunistic Prophylaxis against opportunistic infections if appropriateinfections if appropriate

Appropriate investigations if unwellAppropriate investigations if unwell Reduce perinatal transmissionReduce perinatal transmission

treatment for mothertreatment for mother delivery method delivery method avoidance of breastfeeding (in UK)avoidance of breastfeeding (in UK)

2003/042003/04 5252

Other benefitsOther benefits

Minimise the risk of infecting othersMinimise the risk of infecting others Partner notificationPartner notification Ability to inform important life decisionsAbility to inform important life decisions Relief of anxiety about knowing HIV statusRelief of anxiety about knowing HIV status Access to help from social services, drug Access to help from social services, drug

services etcservices etc

2003/042003/04 5353

Case Presentation 1Case Presentation 1

S.JS.J 26 yr old woman from Sierra Leone26 yr old woman from Sierra Leone Attended GP with 6/52 hist of fever, Attended GP with 6/52 hist of fever,

intermittent cough, cervical lymphadenopathyintermittent cough, cervical lymphadenopathy Nine months previously had seen GP with Nine months previously had seen GP with

fatigue and was found to have mild anaemiafatigue and was found to have mild anaemia Now Rx Penicillin – helped initially but fevers Now Rx Penicillin – helped initially but fevers

returnedreturned

2003/042003/04 5454

Admitted to hospital with PUOAdmitted to hospital with PUO Temp 39 C, P100, BP 85/50Temp 39 C, P100, BP 85/50 LN all areas, 3 cm heparLN all areas, 3 cm hepar Rx multiple ab – no or temp effectRx multiple ab – no or temp effect Reluctantly agreed to HIV test – posReluctantly agreed to HIV test – pos Eventually diagnosed with TB on sputum Eventually diagnosed with TB on sputum

cultureculture Had visited GP regularly over past 9 Had visited GP regularly over past 9

months c/o fatigue / malaise for which only months c/o fatigue / malaise for which only Ix had been FBCIx had been FBC

2003/042003/04 5555


Mr S.S.Mr S.S. 53 yr old salesman, recently separated from 53 yr old salesman, recently separated from

wife since 2000wife since 2000 Unwell for several yrsUnwell for several yrs Admitted Addenbrookes Jan 2006 with ?Admitted Addenbrookes Jan 2006 with ?

EBV/?CMV and abn LFTsEBV/?CMV and abn LFTs Seen by GP June 2007 with fatigue / malaiseSeen by GP June 2007 with fatigue / malaise PancytopeniaPancytopenia

2003/042003/04 5656

Discussed with Haematologist – told Discussed with Haematologist – told “no indication to do HIV test”!“no indication to do HIV test”!

Transferred to different GP in B/STransferred to different GP in B/S Still pancytopeniaStill pancytopenia Now also oral Candida and wt lossNow also oral Candida and wt loss Jan 2008, sent for HIV test – posJan 2008, sent for HIV test – pos CD4 80CD4 80 Started ARV and doing wellStarted ARV and doing well

2003/042003/04 5757


M.C.M.C. 36 year old Zimbabwean woman36 year old Zimbabwean woman Diagnosed March 2007Diagnosed March 2007 CD4 0CD4 0 Spent 41 days in PAH (£6,769)Spent 41 days in PAH (£6,769) Transferred to BLT – further 9 months as Transferred to BLT – further 9 months as

in-patient (£63,720)in-patient (£63,720) Total £70,489Total £70,489 DiedDied

2003/042003/04 5858

The Cost of Late DiagnosisThe Cost of Late Diagnosis

2007: 249 HIV bed-days2007: 249 HIV bed-days 231/249 directly related to late 231/249 directly related to late

diagnosisdiagnosis Total cost Total cost £54,072£54,072 (Cost of HIV test: £3.30)(Cost of HIV test: £3.30)

2003/042003/04 5959

SummarySummary

Natural historyNatural history Benefits of knowing statusBenefits of knowing status Seroconversion Seroconversion Other indicators of HIV infection - when to Other indicators of HIV infection - when to

think of HIVthink of HIV Treatment and monitoringTreatment and monitoring

2003/042003/04 6060

Where to Look for HelpWhere to Look for Help

http://www.medfash.org.ukhttp://www.medfash.org.uk Has produced excellent booklet on HIV Has produced excellent booklet on HIV

in Primary Care available free from in Primary Care available free from websitewebsite

http://www.bhiva.orghttp://www.bhiva.org For testing and treatment guidelinesFor testing and treatment guidelines

2003/041 clinical hiv infection gail crowe princess alexandra hospital

Documents

hiv attendances

hiv testing

overview of hiv

pah slide

uk number of hiv diagnoses

uk annual survey of

yrs old slide

cdc grade slide