5 Case study – male June 2011 – 62 years Partner HIV positive SOB >4 yearsCough ++ minimal sputumOn home oxygenRecurrent chest infection – 2006 to 2011Chronic obstructive airway disease oesophageal candidiasis –
6 Case study – maleStopped 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 entryAb = L = 5cmSpleen – J.P.Discussion
8 Case study – male Prescriptions Tests performed Doxycycline Co-trimoxazoleTests performedFBCU&ELFTHIV – Viral load countCD4 count
10 Case study – make July 2011 Discuss side effects Feeling better Weight gain of 2kg in 3 weeksCough better with DoxycyclineFeels like a drunk when walkingSleep problemsErythematous rashDiscuss side effects
11 Case study – male August 2011 Better No cough Oxygen saturation 98% Right side air entry – good
12 Case study – maleOctober 2012Knee replacementDiscuss surgery in HIV
13 Case study – male January 2013 Erectile dysfunctionDiscuss treatments of erectile dysfunction
16 Case study – male Date CD4 count Viral load cells /ml HAART 19.06.13 180 – 21.4%52Atripla160 – 20.9%<40%160 – 19.0%62160 – 18.0%N/A383100 – 16.9%226140 – 18.2%7,78690 – 17.0%1,469,270
17 Take Home messages The size of the problem CD4 count HIV-1 RNA plasma viral loadOpportunistic Infections and AIDSEra of antiviral therapyNew challengesAdherence, Toxicity, ResistanceThe continued spread of the epidemicProtected Sex
19 Basic principles 4 As a rule of thumb The higher the viral load the faster the disease progressionValues 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 5The 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 thumbCD cells /mm3 normal rangeCD4 > 500 cells /mm3 minimal immune suppressionCD4 ~350 cells /mm3 moderate immune suppressionCD4 <200 cells /mm3 advanced immune suppressionCD4 <50 cells /mm3 severe immune suppression
21 Hepatitis B & C Epidemiology /Prevalence Transmission Acute infection Chronic infectionDiagnosisNatural HistoryTreatment considerationTreatment options
24 Risk of Chronic HBVDepends on nature of immune response to initial infectionVaries according to the age at which the infection is acquiredNeonates – almost 100%Young children – about 50%Adults – about 2-10%ImmunocompromisedMales > 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 positiveAnti–HBc total positive, IgM positive (low titre)HBeAg positive or negative(indicator of viral replication)some variants do not express HBeAgHBV DNA positive
27 Test Results Interpretation Naïve, susceptible HBsAgAnti-HBcAnti-HBsNegativeNaïve, susceptiblePositiveImmune due to natural infectionImmune due to Hepatitis B vaccinationIgM Anti-HBcAcutely infectedPositive or NegativeChronically infectedFour possibilities
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 seroconversionIn HBeAg negative CHB - long term treatment is neededResistance 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 DNAOthers:EntecavirTenofovirEmtricitabineTelbivudine
31 Treatment Life long Monitoring for viral resistance a) genotypic e.g. A181V and N236T for ADVb) virologic a) + >1 log increase in DNAc) clinical a) + b) + ALT riseRegain viral suppression quicker, less clinical decompensation
33 Hepatitis C (HCV) Prevalence It is estimated that up to 250,000 people are infected with HCV in England and Wales1The number of adults diagnosed with CHC is projected to increase four-fold in the next 15 years in the USA and western Europe2The main population subgroups infected with HCV are:1Blood 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 106Albert A, et al. Dig Liver Dis 2004; 36: 646–654.
36 Treatment consideration Goal: clear HCVSecondary aim: reduction in the rate of fibrosis progression?Assessment and progress markersHCV-RNAALTHistologyTreatment of finite durationGenerally poorly tolerated compared to HBV oral agentsDefined as undetectable HCV-RNA in the serum for 6/12 after Tx stopped
37 Predictors of Response to treatment HCV genotype2 > 3 > 5 > 4 >1HCV titrethe lower the betterAmount of liver fibrosisless is betterAgeyounger is probably betterEthnicityinferior response in black patients
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