HIV Grand Round F2

Dr Sris Allan

Consultant GU / HIV Physician

Honorary Associate Professor

June 2011 – 36 year old weighing 64.5Kg

Black African

Abnormal cervical smear

Contraception discussed

Case History – female

On examination

Case study – female

Date CD4 cell count Viral load cells /ml

HAART

09.07.13 400 – 26.5% <40 Atripla

05.03.13 310 – 20.1% <40 Atripla

11.12.12 310 – 20.0% <40 Atripla

28.08.12 340 – 17.0% <40 Atripla

10.05.12 180 – 15.0% <40 Atripla

02.02.12 200 – 11.1% <40 Atripla

20.10.11 180 – 8.0% <60 Atripla

28.07.11 220 – 8.5% 3,401 Atripla

16.06.11 150 – 10.5% N/A N/A

Case study – female

June 2011 – 62 years Partner HIV positive SOB >4 years Cough ++ minimal sputum On home oxygen Recurrent chest infection – 2006 to 2011 Chronic obstructive airway disease

oesophageal candidiasis – 16.06.11

Case study – male

Stopped smoking 2 years ago (smoked 70 to 80 cigarettes per day for 45 years)

Oxygen saturation 92%

Case study – male

On examination

Right sided R.R – 22/min Very poor air entry Ab = L = 5cm Spleen – J.P.

Discussion

Case study – male

Prescriptions Doxycycline Co-trimoxazole

Tests performed FBC U&E LFT HIV – Viral load count CD4 count

Case study – male

HAART

Case study – male

July 2011

Feeling better Weight gain of 2kg in 3 weeks Cough better with Doxycycline Feels like a drunk when walking Sleep problems Erythematous rash

Discuss side effects

Case study – make

August 2011

Better No cough Oxygen saturation 98% Right side air entry – good

Case study – male

October 2012

Knee replacement

Discuss surgery in HIV

Case study – male

January 2013

Erectile dysfunction

Discuss treatments of erectile dysfunction

Case study – male

Date CD4 count Viral load cells /ml

HAART

19.06.13 180 – 21.4% 52 Atripla

26.02.13 160 – 20.9% <40 Atripla

15.11.12 190 -17.0% <40 Atripla

31.07.12 160 – 19.0% 62 Atripla

23.04.12 160 – 18.0% <40 Atripla

23.01.12 N/A 383 Atripla

01.11.11 100 – 16.9% 226 Atripla

01.08.11 140 – 18.2% 7,786 Atripla

22.06.11 90 – 17.0% 1,469,270 Atripla

Case study – male

Take Home messages

The size of the problem CD4 count HIV-1 RNA plasma viral load Opportunistic Infections and AIDS Era of antiviral therapy New challenges Adherence, Toxicity, Resistance The continued spread of the epidemic Protected Sex

Course of HIV infection

Basic principles 4 As a rule of thumb The higher the viral load the faster the disease

progression Values for people not on therapy

< 40 copies per ml Undetectable <1000 copies per ml very low < 100,000 copies per ml low >100,000 copies per ml very high

Basic Principles 5 The clinical presentation of the patient will be related

to the degree of the immune suppression. The CD4 count will gives an indication of the degree

of immune suppression. Rule of thumb CD4 800-1200 cells /mm3 normal range CD4 > 500 cells /mm3 minimal immune

suppression CD4 ~350 cells /mm3 moderate immune

suppression CD4 <200 cells /mm3 advanced immune

suppression CD4 <50 cells /mm3 severe immune

suppression

Hepatitis B & C

Epidemiology /Prevalence Transmission Acute infection Chronic infection Diagnosis Natural History Treatment consideration Treatment options

US CDC, 2006

Acute infection

Risk of Chronic HBV

Depends on nature of immune response to initial infection

Varies according to the age at which the infection is acquiredNeonates – almost 100%Young children – about 50%Adults – about 2-10%

Immunocompromised Males > Females

Diagnosis of chronic HBV

Chronic Hepatitis B is defined as viraemia and hepatic inflammation that persists for > 6 months after acute infection with HBV.

HBsAg positive

Anti–HBc total positive, IgM positive (low titre) HBeAg positive or negative

(indicator of viral replication)

some variants do not express HBeAg HBV DNA positive

Serology of chronic carrier

Test Results Interpretation

HBsAgAnti-HBcAnti-HBs

NegativeNegativeNegative

Naïve, susceptible

HBsAgAnti-HBcAnti-HBs

NegativePositivePositive

Immune due to natural infection

HBsAgAnti-HBcAnti-HBs

NegativeNegativePositive

Immune due to Hepatitis B vaccination

HBsAgAnti-HBc

IgM Anti-HBcAnti-HBs

PositivePositivePositive

Negative

Acutely infected

HBsAgAnti-HBc

IgM Anti-HBcAnti-HBs

PositivePositive

Positive or NegativeNegative

Chronically infected

HBsAgAnti-HBcAnti-HBs

NegativePositive

Negative Four possibilities

Management consideration

PatientLiver healthOccupational health

Baby health

Partner/ close contact

Prevention isbetter than(NO) cure

Monitor & minimiseviral activity

Long term agents Lamivudine Nucleoside reverse transcriptase inhibitor In HBeAg positive CHB - treatment is

generally for one year or more with the aim to bring eAg seroconversion

In HBeAg negative CHB - long term treatment is needed

Resistance is the main problem with long term treatment, more than 60% develop resistance after 3 years of treatment.

Long term agents Adefovir dipivoxil Structurally related to purine base ‘adenine’. Inhibits synthesis of hepatitis B virus DNA

through competition for the enzyme ‘reverse transcriptase’ and incorporation into viral DNA

Others: Entecavir Tenofovir Emtricitabine Telbivudine

Treatment

Life long Monitoring for viral resistance

a) genotypic e.g. A181V and N236T for ADV

b) virologic a) + >1 log increase in DNAc) clinical a) + b) + ALT rise

Regain viral suppression quicker, less clinical decompensation

Hepatitis C: The virus

~50 nm

Hepatitis C (HCV) Prevalence

It is estimated that up to 250,000 people are infected with HCV in England and Wales1

The number of adults diagnosed with CHC is projected to increase four-fold in the next 15 years in the USA and western Europe2

The main population subgroups infected with HCV are:1

Blood donors – 0.04% People attending antenatal clinics in London – 0.4% People attending genitourinary clinics – 1% Intravenous (IV) drug users – 50%

1. NICE technology appraisal guidance 1062. Albert A, et al. Dig Liver Dis 2004; 36: 646–

654.

HCV Natural Historyinfection

chronic hepatitis

cirrhosis

liver failureliver cancer

clearance

20%

20% @ 20 years50% @ 30 years

1.4% pa 3.9% pa

liver transplantation

Treatment consideration Goal: clear HCV Secondary aim: reduction in the rate of fibrosis

progression?

Assessment and progress markersHCV-RNAALT Histology

Treatment of finite duration Generally poorly tolerated compared to HBV oral

agents

Predictors of Response to treatment

HCV genotype2 > 3 > 5 > 4 >1

HCV titrethe lower the better

Amount of liver fibrosisless is better

Ageyounger is probably better

Ethnicityinferior response in black patients