Overview Introduction Diagnosis- Presentation and clinical manifestation Complications and treatment, and Areas of specific concern to anaesthetists

and intensivistsRisks of blood-borne infections, Advice regarding post-exposure prophylaxis INTRODUCTION Human immunodeficiency virus (HIV) - first described in 1981 thro emergence of unusual infexn, pneumocystis C. pneumonia assoc. with candidiasis, in otherwise healthy homosexual men. Of a retrovirus family(2X1 RNA/virion+RT for..,&incorporated,free replicatn. Preferetially infects T helper lymphocytes(CD4 T cells) resulting into a progressive quantitative and qualitative destruction* OI & malignancies. )- identified as belonging to the sub family Lentiviridae two main types, HIV-1 and HIV-2 - demonstrate significant genetic variation. Introduction contd.

50 million people have contracted HIV and 20 million have died worldwide. Prognosis of HIV infxn.- changed dramatically after introduction of antiretroviral drug zidovudine in 1987. Currently, >20 anti-retroviral drugs are available. INTRODUCTION (CONT) HIV patients present anaesthetic problems Challenges High potential for transmission, as dx entity (blood-borne viral infection) Longer survival with treatment Age-related co-morbidities Intensive care demand increasing - reqd for treatment-related side effects and oncological manifestations of the HIV. Drug resistance is increasing MODES OF TRANSMISSION Sexual intercourse(60-70%) MTCT(during P.L&Bf=20-30%) Contaminated bld,bld products and organ donations(3-5%) Contaminated needles(2-3%) RISK GROUPS Therefore from MOT above,the ffl are at risk Promiscuous hetero and homosexuals and partners Pts with STDs

Iv drug users Haemophiliacs Patients 4m endemic areas Botswana,Namibia,SA ,Nigeria esp Benue,Sagamu. Transmission Mostly, during acute phase- viral load is high and the host unaware of infxn. Virus- present in range of body fluids, but considered high risk include blood, semen, vaginal secretions peritoneal fluid, CSF and other cavity fluids Less risk is associated with faeces, nasal secretions, saliva and urine, unless they are contaminated with blood A needlestick injury - associated with a 0.3% chance of seroconversion Hollow needle injuries carry higher risk > solid needle injury bcos larger inoculum is likely. Blood transfusion: Donated blood undergo several levels of screening the first - donor selection In UK, blood is tested for HIV-1 and HIV-2 antibodies ELISA, IFA, FLOW CYTOMETRY In some countries, also screened for HIV p24 antigen. Blood products - heat treated to destroy the virus. Presentation and Clinical Manifestation Initial exposure acute infection (a phase of viral replication & initiation of host immune response). Also called response phase, patient may have a non-specific viral-type illness, probably corresponds to seroconversion This response varies amongst individuals >90% of patients experienced symptoms and signs at this time. Symptoms and signs of acute HIV infection Fever Fatigue Skin rash Myalgia Headache Pharyngitis) Clinical syndromes associated with HIV infection Gastrointestinal Weight loss and malnutrition Gastro-oesophageal reflux common in late disease Diarrhoea bacterial, viral, fungal and parasitic (e.g. cryptosporidium, giardia, Entamoeba histolytica) HIV enteropathy Clinical syndromes associated with HIV infection contd.

Hepatic Hepatitis B, C or D, tuberculosis, fungal (cryptococcus, candida and histoplasmosis) Kaposis sarcoma and lymphoma Ocular Non-infective conjunctivitis, keratitis, haemorrhages, cotton wool spots Infective conjunctivitis, keratitis, retinitis, uveitis Clinical syndromes associated with HIV infection contd. Respiratory Any bacterial infection, Pneumocystis carinii, cytomegalovirus, cryptococcosis, coccidiomycosis, histoplasmosis Tuberculosis (including Mycobacterium avium) Kaposis sarcoma, non-Hodgkins lymphoma Clinical syndromes associated with HIV infection Haematological Peripheral blood cytopenia, anaemia, thrombocytopenia and granulocytopenia Rheumatological Arthralgia, Reiters syndrome, psoriatic arthritis, vasculitis Cardiac Pericardial effusions, non-specific impairment of left-ventricular function, myocarditis Clinical syndromes associated with HIV infection contd Neurological Brain HIV-related meningo-encephalitides infxns including herpes, varicella, cytomegalovirus, Cryptococcal M, Toxoplasma E Toxoplasmosis, cryptococcus, nocardia, tuberculosis, syphilis, Kaposis sarcoma and lymphoma Progressive multi-focal leuco-encephalopathy Spinal cord vacuolar myelopathy, infection Peripheral neurology polyneuropathy, demyelination, neuralgic amyotrophy Clinical syndromes associated with HIV infection contd. Psychological Any of the neurological causes above HIV encephalopathy Renal HIV nephropathy (glomerular disease) Oral problems Candidiasis, herpes simplex, varicella zoster Gingivitis, periodontitis Kaposis sarcoma Making Diagnosis Clinical features Acute phase: Antibodies to HIV-1 demonstrable using Enzyme-linked immunosorbent assay (ELISA), IFA

Now Rapid HIV Ab Test Western blot techniques., HIV-1 and HIV-2 Abs - weakly positive or non-reactive, test misinterpreted as negative (false Negative) False positive rate - 25% reported therefore all tests shd be repeated. Then confirmation test (when seroconversion occurs later in the disease process). Using DETECTION OF HIV-1 RNA OR VIRAL P24 ANTIGEN,(DETECTABLE 28 WEEKS POST INITIAL INFECTION) RNA CONCENTRATIONS - 13 106 RNA COPIES/ML MAY BE DETECTED. DURING ACUTE PHASE- CD4 COUNT OFTEN s, THEN FOLLOWED BY EXPANSION OF T- CELLS CD8 POPULATION, THEREBY ALTERING CD4/CD8 RATIO @ ABOUT DAY 16 AFTER THE ACUTE PHASE. EXPANSION OF CD8 CYTOTOXIC T-CELL SUBGRP PROBABLY ASSOC. WITH ANTIVIRAL ACTIVITY. Treatment & Prognosis Post initial infxn - viraemia and immune response equilibrate at a set-point Possible relationship b/w viral load @ this stage and prognosis: patient with low load - better prognosis than pt. with a high persistent load. Timing of starting HAART is controversial, but this therapy is not recommended in asymptomatic patients with CD4 counts above 350 cells/mm3. Initial regimens, usually two nucleoside analogue reverse transcriptase inhibitors(NRTIs) plus either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor. Drugs Nucleoside reverse transcriptase inhibitors (NRTI)Zidovudine Lamivudine - as monotherapy, limited effect in suppressing HIV except in the area of maternofetal transmission. Results in the emergence of resistance. Side effect profile includes:gastrointestinal problems - diarrhoea, vomiting & pancreatitis. Lactic acidosis, hepatic steatosis and liver failure peripheral neuropathy. Non-nucleoside reverse transcriptase inhibitors (nNRTIs) Nevirapine Efavirenz Loviride bind only to HIV-1 reverse transcriptase. Protease inhibitors (PIs) HIV-1 protease is an enzyme essential for viral replication acts @ the point at which virions become mature. Treatment results in the release of immature viruses that are non-infectious and can be eliminated. Viral load- often reduced to levels that are undetectable. Include:

Indinavir Saquinavir Ritonavir Introduced in 1995 particularly effective when used in conjunction with NRTIs. The drug acts on maturing virus particles, thus it does not have any impact on CD4 T-cells . The drug prevent spread of infection. Use of dual therapy seems to improve CD4 counts and reduce viral load. PIs - are metabolized by P450 system also either inhibit or induce cytochrome P450 isoenzymes, thus potential for drug interaction. Wide range of side effects:Onset of type 2 diabetes and insulin resistance DM Fatty deposition in neck (buffalo hump) Peripheral lipodystrophy, hyperlipidaemia Gastrointestinal problems - NVD Raised creatine phosphokinase, hepatic transaminases (saquinavir) Circumoral and peripheral paraesthesia (ritonavir) Hepatitis with raised transaminases and bilirubin (indinavir) Mitochondrial toxicities (non-specific) Fusion inhibitors prevent entry of the virus into the cell. Currently, only Enfuvirtide is licensed in the UK. Treatment Impact Dramatic alteration in pattern and natural hx of HIV infxn Decreased hosp. admissions and Fewer opportunistic infections. Studies Findings suggest that even with an imperceptible viral load THERE IS STILL AN INFECTIVE RISK HIV and anaesthesia 2025% of HIV-+ pts will require surg during their illness. useful to consider the difficulties that HIV poses for anaesthesia Areas of specific concern to anaesthetists & intensivists General problems of the disease, Local problems of HIV or infection, Drug therapy Non-specific considerations of dealing with a potentially infective condition General problems Include:Pts chronic health status - malnourished and wasted palsma protein and drug handlings Haematological, hepatic or renal problems. Drug therapy side effects may also add to anaesth. considerations Patients with dementia - increased sensitivity to sedation & psychoactive drugs, opioids, benzodiazepines and neuroleptics. Hyperkalaemia is a potential risk to be considered in the pt with progressive myopathy or neuropathy. Pain control in these pts is an increasing problem, either due to the dx, the

opportunistic infxns or Rx therapy. Local manifestations Provide technical difficulties for anaesthesia. Chronic respiratory problems may alter oxygenation, particularly in those who have had pneumocystis C. pneumonia (PCP) and on prophylaxis. Airway problems caused by Kaposis sarcoma, not uncommon. Obstetric Anaesthesia Vertical transmission in untreated HIV-1 infected mothers 25% of pregnancies 60% of the transmissions occur during delivery 35% during breastfeeding. Elective Caesarean section + antiretroviral Rx dramatically decreases transmission. Controversy , in these patients, over postop events. Some studies indicate a higher complication rate Others show no difference compared with vaginal birth. In pts with CD4 count < 500 cc/l, post-CS morbidity is higher. In the use of blood patches if dural puncture occurs, few data exist that failed to show any morbidity attributable to use of blood patches. Regional Anaesthesia Currently, no evidence to suggest that complications ffn epidural are higher in HIV-positive pts compared with other pt grps Regional techniques are not C/I Neurological examn should be comprehensive, documenting any Neurological deficit in the pts notes. Increased ICP However, in CNS infections, (meningitis and encephalopathy),myelopathy, vertebral or spinal neoplasms,coagulopathy, all of which may complicate HIV infection, neuroaxial technqs are C/I. Anaesthetic Management Plan A multisystemic and multidisciplinary approach is recommended. Thorough preop assessmnt to determine the status of HIV infection & this involves -history,including the risk factors -PE -Lab tests -Assessmnt of organ involvement -Drug hx & side effects. Anaesthetic Management Plan cond. Investigations should include : -FBC -Clotting profile

-biochemical tests- glucose,electrolytes,renal & LFTs viral load & CD4 Count -CXR to screen for opportunistic chest infections. -ECG & Echo(if possible) to screen for cardiomyopathy. Anaesthetic Management cond. PREPARATION FOR THEATRE AND PERSONEL: -Universal precaution: with gloves , aprons etc,sharp object collection device -staff fully educated and aware of protocols in the event of occupational exposure. -availability of post exposure prophylaxis

Perioperative Considerations Minimise interruptions in ARV therapy as possible to diminish drug resistance. Consider drug interactions with ARV with use of drugs affected by hepatic enzyme inhibition and or induction. Strict aseptic techniques to be exercised as HIV infected patients are immunocompromised and are susceptible to bacterial infections. THE ANAESTHETIC PLAN SHOULD BE TAILORED TO THE INDIVIDUAL PATIENT AND THE TYPE OF SURGERY AS APPROPRIATE. Infective Patients Problems of dealing with potentially infective pts are those of equipment contamination Sensible and hygienic approaches to help reduce risk of transmission include:Cleaning, Sterilization and Using devices such as filters on anaesthetic circuits(HMEs with Filters) Age-Related Co-morbidities As survival times are improving, there is common age-related co-morbidities in HIV pts. Accelerated arteriosclerosis may Ischaemic coronary syndromes. Re-stenosis rates ffn percutaneous coronary artery stenting is higher in HIV pts than in non-HIV pts. HIV and Intensive Care Pts with HIV can present to the ICU ffn Surgery Trauma Any medical problem- Neurological & Gastroenterological presentations are common Mgt shd be the same as for other pts. Mortality of HIV-positive pts admitted to ICU has from 70% at the beginning of the pandemic to currently about 39% in Nigeria.

Factors associated with mortality and reqmnt of mechanical ventilation are Low serum albumin Oncotic-induced pulm oedema or Diagnosis of pneumocystis C. pneumonia (PCP) Bact infxns and sepsis + opportunistic infxns- increasingly seen. 10 presentation with Pneumocystis carinii was common but is less so now due to Early diag, intro of CPT . When this dx does present it is usually in undiagnosed pts. TB shd always be considered & is an problem Prognosis is determined by The condition, The chronic health status of the pt Their immune system(CD4 Count very important) Appropriate Rx Prognosis appears to be worse in pts who fail to respond to appropriate Rx in the first few days. E.g pneumocystis pneumonia, unresponsive after 45 days of aggressive Rx has very poor prognosis

Cotrimoxazole Preventive Therapy (CPT) prevention of several 20 bacterial and parasitic infxns On the is Rxt-related complications resulting in ICU admissions. These include Antiretroviral-related toxicity, Hypersensitivity (StevensJohnson syndrome and toxic epidermal necrolysis, TEN) and Immune reconstitution inflammatory syndrome (IRIS), a life-threatening rxn, usually seen from days to weeks after initiation of HAART, xtized by Paradoxical worsening of symptoms and Aggravation of ongoing infxns, including fever, hypoxaemia, an in radiographic infiltrate & adenomegalies Antiretroviral Treatment in ICU Initiation of antiretroviral Rx is hazardous because of risk of IRIS Rx beneficial in Improving prognosis and reducing viral replication. Antiretroviral Rx appears to reduce mortality in Pts newly diagnosed with HIV admitted with PCP. Pts with CD4 counts below 200 cells/l and Those whose admission is AIDS-related - should be considered for antiretroviral Rx. Currently, only zidovudine is available as an intravenous prepn. May be difficult to maintain HAART if the gut is non functional to sub-therapeutic dosage and consequent emergence of resistance Recent recommendations suggest Maintaining Rx, if possible, in those with undetectable plasma HIV RNA. Close consultation with HIV specialists, pharmacists, and The use of blood-level determinations, if available. HIV and Anaesthetists The risk of contracting HIV infxn at work is perceived to be low, although HIV is a blood-borne agent and transmission is possible. Sensible precautions such as

Wearing gloves, Attention to hygiene and Avoidance of sharps injuries by careful practice Are all advocated. Exposure to fluids or blood that might be infected constitutes an exposure and should be treated seriously. Health-worker Exposure to HIV Specialist advice should be sought immediately It is likely that post-exposure prophylaxis would be implemented rapidly (within 12 hours, latest 72 hrs). This should always be done with guidance from an HIV specialist. Currently, post-exposure prophylaxis (PEP) consists of a combination of Two NRTI drugs- Zidovudine and Lamivudine added to A protease inhibitor (PI) POST EXPOSURE PROPHYLAXIS (PEP) At Risk Personnel Students, Laboratorians Surgeons Anaesthetists Nurses Attending clinicians, Public-safety workers, Categories of Exposures Ist Degree ExposuresBlood and blood stained body fluid A percutaneous injury (e.g., a needlestick or cut with a sharp object) Contact of mucous membrane or exposed skin that is chapped, abraded, or afflicted with dermatitis. Any direct contact (i.e., contact without barrier protection) to concentrated virus in a research laboratory or production facility Second Degree Exposures Semen Vaginal secretions Cerebrospinal fluid, Synovial fluid, Pleural fluid, Peritoneal fluid, Pericardial fluid, and Amniotic fluid. Breast milk Third Degree Exposures Feaces, Nasal secretions,

Saliva, sputum, Sweat, Tears, Urine, and Vomitus NB: Not considered potentially infectious unless they contain bld Risk for transmission of HBV, HCV, and HIV infxn from these fluids and materials is extremely low ACCIDENTAL EXPOSURE 1- DEFINITION - Accidental contact with blood or a contaminated body (biological) fluid - Contact may be through skin (puncture or cut) or spillage on mucous membrane or broken skin RISK FACTORS Use of open bore needle Depth or size of wound Duration of contact Status of source Absence of protective personal clothing Risky procedures: capping of needles +++, venepuncture, intravenous cannulation, blood culture RISK FACTORS Source of exposure Person exposed: victim Type of infectious agent : virus, bacteria, parasites, Degree of risk : HIV: 0.30 % (puncture); 0.03 % (splash) Hep B: 30 % Hep C: 3 % PRIMARY PREVENTION Development & dissemination of Universal Safety Precautions (USP) to all staff (POSTER ++, educative materials) Facilities for practice of USP :Soap cake or liquid Fenestrated Soap dishes Running water or bucket & Ladle full of clean fresh water One-use towels disposable paper towels

Minimum Standard Precautions assume all patients are HIV + Routine hand washing before and after contact with any pt. Use Barrier precautions disposable gloves for routines and procedures Health workers to cover cuts, bruises and rashes on their body-adhesive plaster or bandages Safe handling & disposal of sharp instruments /equipments Single-use disposable syringes/Needles Do NOT RECAP needles after use Discard used N/S in a puncture-resistant container (sharp Box) Strict compliance with USP. Appropriate disposal of material POST EXPOSURE PROPHYLAXIS (PEP) 1- IMMEDIATE MANAGEMENT (5 MINUTES) Puncture, injury or contact with broken skin Do not squeeze affected area Wash with soap and water copiously Rinse liberally and dry Apply disinfectant (if available) 70% alcohol, Polyvidone Iodine 0.5% Na Hypochlorite Polyhexidine 6% Hydrogen peroxide 2% Glutarylaldehyde For about 5 minutes IMMEDIATE CARE II Mucous membranes or eyes Rinse liberally with water or physiological solution For 5 to 10 minutes RISK ASSESSMENT (4 HOURS) There shd be designated accidental exposure unit High risk Deep puncture wound with open bore needle Cut with a scalpel Exposure to high concentration of HIV (laboratory) Intermediate risk Superficial puncture with an open bore needle Superficial cut with a scalpel Deep puncture by intramuscular or subcutaneous injection Low risk Superficial erosion of skin by a suture needle or s/c injection ACCIDENT REPORTING (within 24 hours)

Accidental occupational exposure Report to: Staff doctor Head of department Head of institution Analyse circumstances of accident To determine degree of exposure To determine attendant risk Future prevention PROPHYLACTIC ARV (4 to 48 hours) ARV according to existing guidelines Combination therapy: eg. 2NNRTI + 1PI Toxicity and precautions Contra indications (2 situations) Refusal Hx of drug hypersensitivity rxn MEDICAL AND BIOLOGICAL FOLLOW-UP (for 6 months) Counseling Blood tests within 8 days for source and victim HIV Hep B Hep C Transaminases Further tests 6 weeks 3 months 6 months Where PCR is available, shorter test interval (within a week) is possible Medical report by staff doctor - after final blood test (6 months) Risk of an HIV-infected healthcare worker transmitting the dx to a pt is considered to be very low provided the healthcare worker does not carry out exposure-prone procedures (EPPs) Are procedures where the healthcare worker is at risk of injury with sharp instruments or needles, within an open body-cavity and where the operators hands may not be visible. If the healthcare worker is then injured the patient will be exposed to infected bld. The Future New generations of drugs e.g. Viral-maturation inhibitors and HIV-integrase inhibitors May be more effective and have fewer side effects. These improvements may the incidence of pt non-compliance.

IN CONCLUSION. HIV/AIDS is no longer rare, and all clinicians shd have a working knowledge of its presentation and management. Given that 25% of HIV infected patients would require surgery during the time of their illness,it is important for anaesthetists to understand the implications of anaesthesia in HIV infected patients. This requires: -basic understanding of HIV infection itself -the clinical symptoms and organ involvement -pharmacology of ARVs -implications for RA ;and -issues surrounding infection control. References Avidan MS, Jones N, Pozniak AL. The implications of HIV for the anaesthetist and the intensivist. Anaesthesia 2000; 55: 34454. Evron S, Glezerman M, Harow E, et al. Human immunodeficiency virus: anesthetic and obstetric considerations. Anesth Analg 2004; 98: 50311. Sabin CA, Phillips AN, Yee TT, et al. Twenty five years of HIV infection in haemophilic men in Britain: an observational study. Br Med J 2005; 331: 9978. Tindall B, Barker S, Donovan B, et al. Characterisation of the acute illness associated with human immunodeficiency virus infection. Arch Intern Med 1988; 148: 9459.