HIV Grand Round F2

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HIV Grand Round F2

• Dr Sris Allan
• Consultant GU / HIV Physician
• Honorary Associate Professor

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Case History female

• June 2011 36 year old weighing 64.5Kg
• Black African
• Abnormal cervical smear
• Contraception discussed

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Case study female

• On examination

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Case study female
Date CD4 cell count Viral load cells /ml HAART
09.07.13 400 26.5 lt40 Atripla
05.03.13 310 20.1 lt40 Atripla
11.12.12 310 20.0 lt40 Atripla
28.08.12 340 17.0 lt40 Atripla
10.05.12 180 15.0 lt40 Atripla
02.02.12 200 11.1 lt40 Atripla
20.10.11 180 8.0 lt60 Atripla
28.07.11 220 8.5 3,401 Atripla
16.06.11 150 10.5 N/A N/A
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Case study male

• June 2011 62 years
• Partner HIV positive
• SOB gt4 years
• Cough minimal sputum
• On home oxygen
• Recurrent chest infection 2006 to 2011
• Chronic obstructive airway disease
  oesophageal candidiasis 16.06.11

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Case study male

• Stopped smoking 2 years ago (smoked 70 to 80
  cigarettes per day for 45 years)
• Oxygen saturation 92

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Case study male

• On examination
• Right sided R.R 22/min
• Very poor air entry
• Ab L 5cm
• Spleen J.P.
• Discussion

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Case study male

• Prescriptions
• Doxycycline
• Co-trimoxazole
• Tests performed
• FBC
• UE
• LFT
• HIV Viral load count
• CD4 count

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Case study male

• HAART

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Case study make

• 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

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Case study male

• August 2011
• Better
• No cough
• Oxygen saturation 98
• Right side air entry good

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Case study male

• October 2012
• Knee replacement
• Discuss surgery in HIV

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Case study male

• January 2013
• Erectile dysfunction
• Discuss treatments of erectile dysfunction

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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 lt40 Atripla
15.11.12 190 -17.0 lt40 Atripla
31.07.12 160 19.0 62 Atripla
23.04.12 160 18.0 lt40 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
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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

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Course of HIV infection
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Basic principles 4

• As a rule of thumb
• The higher the viral load the faster the disease
  progression
• Values for people not on therapy
• lt 40 copies per ml ? Undetectable
• lt1000 copies per ml ? very low
• lt 100,000 copies per ml ? low
• gt100,000 copies per ml ? very high

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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 gt 500 cells /mm3 ? minimal immune
  suppression
• CD4 350 cells /mm3 ? moderate immune
  suppression
• CD4 lt200 cells /mm3 ? advanced immune
  suppression
• CD4 lt50 cells /mm3 ? severe immune
  suppression

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Hepatitis B C

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

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US CDC, 2006
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Acute infection
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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 gt Females

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Diagnosis of chronic HBV

• Chronic Hepatitis B is defined as viraemia and
  hepatic inflammation that persists for gt 6 months
  after acute infection with HBV.
• HBsAg positive
• AntiHBc total positive, IgM positive (low titre)
• HBeAg positive or negative
• (indicator of viral replication)
• some variants do not express HBeAg
• HBV DNA positive

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Serology of chronic carrier
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Test Results Interpretation
HBsAg Anti-HBc Anti-HBs Negative Negative Negative Naïve, susceptible
HBsAg Anti-HBc Anti-HBs Negative Positive Positive Immune due to natural infection
HBsAg Anti-HBc Anti-HBs Negative Negative Positive Immune due to Hepatitis B vaccination
HBsAg Anti-HBc IgM Anti-HBc Anti-HBs Positive Positive Positive Negative Acutely infected
HBsAg Anti-HBc IgM Anti-HBc Anti-HBs Positive Positive Positive or Negative Negative Chronically infected
HBsAg Anti-HBc Anti-HBs Negative Positive Negative Four possibilities
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Management consideration
Monitor minimise viral activity

• Patient
• Liver health
• Occupational health
• Baby health
• Partner/ close contact

Prevention is better than (NO) cure
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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.

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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

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Treatment

• Life long
• Monitoring for viral resistance
• a) genotypic e.g. A181V and N236T for ADV
• b) virologic a) gt1 log increase in DNA
• c) clinical a) b) ALT rise
• Regain viral suppression quicker, less clinical
  decompensation

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Hepatitis C The virus
50 nm
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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
  are1
• 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 106
2. Albert A, et al. Dig Liver Dis 2004 36 646654.

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HCV Natural History
infection
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clearance
chronic hepatitis
20 _at_ 20 years 50 _at_ 30 years
cirrhosis
3.9 pa
1.4 pa
liver failure
liver cancer
liver transplantation
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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

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Predictors of Response to treatment

• HCV genotype
• 2 gt 3 gt 5 gt 4 gt1
• HCV titre
• the lower the better
• Amount of liver fibrosis
• less is better
• Age
• younger is probably better
• Ethnicity
• inferior response in black patients