1. HIV Grand Round F2 Dr Sris Allan Consultant GU / HIV Physician
Honorary Associate Professor

2. Case History – female June 2011 – 36 year old weighing 64.5Kg
Black African
Abnormal cervical smear
Contraception discussed

3. Case study – female
On examination

4. Case study – female Date CD4 cell count Viral load cells /ml HAART
400 – 26.5%
<40
Atripla
310 – 20.1%
310 – 20.0%
340 – 17.0%
180 – 15.0%
200 – 11.1%
180 – 8.0%
<60
220 – 8.5%
3,401
150 – 10.5%
N/A

5. Case study – male 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 –

6. Case study – male
Stopped smoking 2 years ago (smoked 70 to 80 cigarettes per day for 45 years)
Oxygen saturation 92%

7. Case study – male On examination Discussion Right sided R.R – 22/min
Very poor air entry
Ab = L = 5cm
Spleen – J.P.
Discussion

8. Case study – male Prescriptions Tests performed Doxycycline
Co-trimoxazole
Tests performed
FBC
U&E
LFT
HIV – Viral load count
CD4 count

9. Case study – male
HAART

10. Case study – make July 2011 Discuss side effects 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

11. Case study – male August 2011 Better No cough Oxygen saturation 98%
Right side air entry – good

12. Case study – male
October 2012
Knee replacement
Discuss surgery in HIV

13. Case study – male January 2013
Erectile dysfunction
Discuss treatments of erectile dysfunction

16. Case study – male Date CD4 count Viral load cells /ml HAART 19.06.13
180 – 21.4% 52
Atripla
160 – 20.9%
<40 %
160 – 19.0% 62
160 – 18.0%
N/A
383
100 – 16.9%
226
140 – 18.2%
7,786
90 – 17.0%
1,469,270

17. 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

18. Course of HIV infection

19. 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

20. 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
CD 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

21. Hepatitis B & C Epidemiology /Prevalence Transmission Acute infection
Chronic infection
Diagnosis
Natural History
Treatment consideration
Treatment options

22. US CDC, 2006

23. Acute infection

24. Risk of Chronic HBV
Depends on nature of immune response to initial infection
Varies according to the age at which the infection is acquired
Neonates – almost 100%
Young children – about 50%
Adults – about 2-10%
Immunocompromised
Males > Females

25. 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

26. Serology of chronic carrier

27. Test Results Interpretation Naïve, susceptible
HBsAg
Anti-HBc
Anti-HBs
Negative
Naïve, susceptible
Positive
Immune due to natural infection
Immune due to Hepatitis B vaccination
IgM Anti-HBc
Acutely infected
Positive or Negative
Chronically infected
Four possibilities

28. Management consideration
Monitor & minimise
viral activity
Patient
Liver health
Occupational health
Baby health
Partner/ close contact
Prevention is
better than
(NO) cure

29. 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.

30. 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

31. Treatment Life long Monitoring for viral resistance
a) genotypic e.g. A181V and N236T for ADV
b) virologic a) + >1 log increase in DNA
c) clinical a) + b) + ALT rise
Regain viral suppression quicker, less clinical decompensation

32. Hepatitis C: The virus
~50 nm

33. 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%
NICE technology appraisal guidance 106
Albert A, et al. Dig Liver Dis 2004; 36: 646–654.

35. HCV Natural History infection clearance chronic hepatitis cirrhosis
20%
clearance
chronic hepatitis
20 years
30 years
cirrhosis
3.9% pa
1.4% pa
liver failure
liver cancer
liver transplantation

36. Treatment consideration
Goal: clear HCV
Secondary aim: reduction in the rate of fibrosis progression?
Assessment and progress markers
HCV-RNA
ALT
Histology
Treatment of finite duration
Generally poorly tolerated compared to HBV oral agents
Defined as undetectable HCV-RNA in the serum for 6/12 after Tx stopped

37. Predictors of Response to treatment
HCV genotype
2 > 3 > 5 > 4 >1
HCV titre
the lower the better
Amount of liver fibrosis
less is better
Age
younger is probably better
Ethnicity
inferior response in black patients