HIV & AIDS

YP Beh

ST6 GUM

Coventry & Warwickshire PT

19.6.12

Objectives Biology of HIV Virus Epidemiology Clinical Presentations HIV Testing HIV and Antiretroviral Treatment Chronic HIV associated conditions HIV and Pregnancy Post exposure prophylaxis for HIV

Biology of HIV 1 HIV is a retrovirus It cannot replicate by itself and must utilise host cell machinery

in order to produce new virus particles It can convert its RNA genome into DNA HIV DNA integration into the host cell genome allows it to

access host biochemical pathways to reproduce The RNA – DNA reaction is catalysed by reverse transcriptase HIV DNA is subsequently integrated into the host cell’s genome

HIV life cycle http://highered.mcgraw-hill.com/sites/0072

495855/student_view0/chapter24/animation__how_the_hiv_infection_cycle_works.html

CD4 & Viral Load

• CD4 Lymphocyte count• Normal Value 500 -1200 cells

• Indication ‘strength’ of the immune system• AIDS if CD4 less than 200 cells

• Viral Load• The amount of HIV Virus in the blood• Measurement of viral copies/ml

Estimated number of people living with HIV infection: United Kingdom, 2010

Total with HIV = 91,500 (85,400 − 99,000)

Total diagnosed = 69,250 (67,800 − 70,800)

Total undiagnosed = 22,200 (16,350 − 29,650)

New HIV diagnoses by exposure group: United Kingdom, 2001 – 2010

Probable recent infection among people newly diagnosed with HIV by exposure group: England and Northern Ireland, 2010

New HIV diagnoses by probable country of infection : 2001-2010

18%

40%

34%

29% 28%

39%

63%

58%

46%50%

0%

10%

20%

30%

40%

50%

60%

70%

MSM Heterosexual men Heterosexual women People who inject drugs

Overall

Prop

orti

on d

iagn

osed

late

CD4 <200

CD4 <350

Late diagnoses of HIV by exposure group: UK, 2010

Presentations of HIV Asymptomatic

Seroconversion period

AIDS-related conditions

Chronic HIV-associated conditions

HIV Seroconversion

Primary HIV Infection Two – four weeks post-infection Symptoms

• Fever, maculopapular rash, myalgia, pharyngitis, headache, lymphadenopathy

• Varies from very mild to severe enough to require hospital admission

Be aware in high-risk groups! Highly infectious time because of high viral load Transient fall in CD4 count can lead to OI

HIV and the Lung Infections

• Tuberculosis• Pneumocystis jiroveci pneumonia• Fungal pneumonia• Bacterial pneumonia

Malignancy• Kaposi’s sarcoma• Lymphoma

Non-malignant conditions• Lymphoid interstitial pneumonitis

Pulmonary Infections - PCP

Pulmonary Infections - TB

Lymph nodes TB Lymphoma HIV

HIV and the Brain Opportunistic infections

• Toxoplasma gondii - abscesses and encephalitis (<200)• Cryptococcus neoformans - meningitis (<200)• JC virus – Progressive Multifocal Leucoencephalopathy

(<100)• CMV - retinitis, encephalitis, mononeuritis multiplex,

cauda equina syndrome Tumours

• Primary CNS lymphoma HIV-related disorders

• HIV-associated dementia complex• Peripheral neuropathy (distal sensory polyneuropathy)

Progressive multi-focal leuco- encephalopathy (PML)

Cryptococcoma

HIV & Eye

infection

Retinitis

HIV and the Gut Oesophageal candidiasis Infective Diarrhoea

• Bacteria e.g. campylobacter, shigella, MAI• Protozoa e.g. cryptosporidium, isospora belli,

microsporidium• Viruses e.g. CMV, adenovirus

Malignancy• Kaposis sarcoma

Drug Side-Effects HIV Wasting Syndrome

Oesophageal candidiasis

HIV and the Skin

Seborrhoeic dermatitis Aphthous ulceration Oral candida (<300) Kaposi’s Sarcoma (<200) Bacteria:

• Impetigo, folliculitis Fungi

• Tinea pedis, cruris; pityriasis versicolor

• Candida - genital, perianal, other

Viruses• HSV 1 and 2 • Varicella zoster • EBV (<300)• HPV • Molluscum

contagiosum Neoplasia

• Cervical dysplasia

Kaposi’s sarcoma

Who should be tested?

Opt Out’ for: All patients attending GUM or sexual health clinics. All women attending antenatal services. All women attending termination of pregnancy

services. All patients registering with drug dependency

programmes reporting a history of injecting drug use. All patients diagnosed with Tuberculosis, Hepatitis B,

Hepatitis C and Lymphoma.

HIV Testing 4th generation tests

eg Determine test Antigen & Antibody

detection

Previous 3rd gen tests Antibody only (INSTI)

All must be confirmed by formal venepuncture

BASHH Statement on HIV window period

4th generation tests are recommended which test for HIV antibodies and p24 antigen simultaneously

They will detect the great majority of individuals who have been infected with HIV 4 weeks after exposure

A negative result at 4 weeks post exposure is very reassuring

An additional HIV test should be offered to all persons at 3 months to definitively exclude HIV infection

Highly Active Anti-Retroviral Therapy (HAART)

Suppress Viral Load & Increases CD4

Combination therapy

HAART Initiation when CD4 <350cells/mm3

Reduced risk of disease progression Life expectancy

Late 90s Now

HAART & the HIV Life Cycle

When to start?

BHIVA guideline 2008

Chronic HIV-Associated Conditions

Triant VA,et al. J Clin Endocrinol Metab. 2007;92:2506-2512.

Rate of Heart Attacks in HIV Positive and HIV Negative Patients

Age Group (Years)

Eve

nts

per

10

00 P

erso

n-Y

ears

20

40

60

80

100

0

18-34 35-44 45-54 55-64 65-74

HIV+

HIV–

Age

SmokingBlood pressure

CholesterolHAART

HIV

Heart Disease

HIV and Hepatitis B 100 times more infectious than HIV 10 times more infectious than HCV Lives outside the body for up to 7 days

Progression of Chronic Hepatitis

Adapted from: Fattovich, et al. Gastroenterology. 2004;127:S35-S50. Torresi, et al. Gastroenterology. 2000;118:S83-S103. Fattovich, et al. Hepatology. 1995;21:77-82. Perrillo, et al. Hepatology. 2001;33:424-432.

Chronic Infection

Cirrhosis

Liver Failure

Liver Cancer (HCC)

Death30%

23% in 5 yr

Liver Transplantation

10%–15% in 5 yr

5%–10%

HIV & Bone Disease: Greater risk of fractures in HIV-Infected individuals

0

0.5

1

1.5

2

2.5

3

All Vertebral Hip Wrist

HIV non-HIV

p<0.001

Fra

ctur

e pr

eval

ence

/100

per

sons

Triant VA, Brown TT, Lee H, Grinspoon SK. Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 2008; 93:3499–3504

Other chronic co-morbidities with HIV Cancer

Kidney Disease Renal function slowly declines with age

Diabetes

Neurocognitive decline

HIV and Pregnancy – Reducing VL When to treat

• Continue treatment if conception occurs on HAART• Between 20/40 and 28/40• Aim for undetectable VL by 36/40

What to treat with• At least 3 drugs – usually combivir + PIs• ZDV monotherapy

HIV and Pregnancy – Post-Delivery Therapy for baby

• 4/52 triple therapy for babies born to mothers with detectable VL

• 4/52 ZDV for babies born to mothers with undetectable VL

Recommend EXCLUSIVE formula feeding

Testing baby• Loss of maternal antibody at 18/12• PCR testing; primers to amplify maternal virus

Post-Exposure Prophylaxis PEP consists of 28 days of triple therapy Not licensed Offered only where the risk is high Should be offered within 72 hours Best result within 1 hour of the contact Reduces the risk of transmission by 80% Common side effects are nausea, diarrhoea and

fatigue Less common side effects are renal dysfunction, insulin

resistance, lipid disorders

HIV TransmissionType of exposure Estimated risk of HIV transmission

per exposure

Receptive anal intercourse 0.1-3.0%

Receptive vaginal intercourse 0.1%-0.2%

Insertive vaginal intercourse 0.03%-0.09%

Insertive anal intercourse 0.06%

Receptive oral sex (fellatio) 0-0.04%

Needle–stick injury 0.3%

Sharing injecting equipment 0.67%

Mucous membrane exposure 0.09%

Recommended information sources

ABC of AIDS, BMJ Books www.BHIVA.com www.aidsmap.com http://www.hiv-druginteractions.org/ www.medscape.com

Summary HIV is a treatable condition

Can present with any symptom, or none

People living with HIV in the UK can expect a near-normal life expectancy

Importance of diagnosing early infection

Questions Thank you.