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HIV Grand Round F2. Dr Sris Allan Consultant GU / HIV Physician Honorary Associate Professor. Case History – female. June 2011 – 36 year old weighing 64.5Kg Black African Abnormal cervical smear Contraception discussed. Case study – female. On examination. Case study – female.
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HIV Grand Round F2 Dr Sris Allan Consultant GU / HIV Physician Honorary Associate Professor
Case History – female • June 2011 – 36 year old weighing 64.5Kg • Black African • Abnormal cervical smear • Contraception discussed
Case study – female • On examination
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 – 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 – 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
Case study – male • 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
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
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
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
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
Management consideration Monitor & minimise viral activity • Patient Liver health Occupational health • Baby health • Partner/ close contact Prevention is better than (NO) cure
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 DNA c) 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% • NICE technology appraisal guidance 106 • Albert A, et al. Dig Liver Dis 2004; 36: 646–654.
HCV Natural History infection 20% clearance chronic hepatitis 20% @ 20 years 50% @ 30 years cirrhosis 3.9% pa 1.4% pa liver failure liver cancer liver transplantation
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
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