Microbiology 2 Flashcards

Question

what are features of HIV-1 and HIV-2? where are they most prevalent?

Answer 1

- HIV-1 is the most frequently occurring strain globally - HIV-2 is almost entirely confined to West Africa; some spread to Europe, esp. France and Portugal - HIV-2 has only 40% structural homology with HIV-1; it's associated with immunosuppression and AIDS, and takes a more indolent course than HIV-1 - most drugs used in HIV-1 are ineffective in HIV-2

Answer 2

- two molecules of single-stranded RNA are within the nucleus - reverse transcriptase polymerase converts viral RNA into DNA (characteristic of retroviruses) - protease includes integrase (p32 and p10) - p24 (core protein) levels can be used to monitor HIV disease - p17 is the matrix protein - gp120 is the outer envelope glycoprotein which binds to cell surface CD4 molecules - gp41 is a transmembrane protein, influences infectivity and cell fusion capacity

Answer 3

integrase (p32 and p10)

Answer 4

p24 (core protein) levels can be used to monitor HIV disease

Answer 5

gp160 = gp120 and gp41 (envelope) - gp120 is the outer membrane glycoprotein which binds to cell surface CD4 molecules - gp41 is a transmembrane protein indluences infectivity and cell fusion capacity

Answer 6

- characterised by possession of the enzyme reverse transcriptase, which allows viral RNA to be transcribed into DNA and incorporated into the host cell genome

Answer 7

- enzyme - allows viral RNA to be transcribed into DNA and thence incorporated into the host cell genome - error-prone process with significant rate of mis-incorporation of bases; this, with a high rate of viral turnover, leads to genetic variation and diversity of viral subtypes/clades

Answer 8

- represent four independent cross species transfers - three (M, N and O) based on chimpanzee related strains of SIV - one (P) represents chimpanzee to gorilla to human transmission

Answer 9

- 98% of infections worldwide - high degree of diversity - subtypes denoted A-K - predominance of subtype B in Europe, North America and Australia - areas of Central and sub-Saharan Africa have multiple M subtypes - clade C is the commonest subtype - recombination of viral material generates an array of circulating recombinant forms (CRFs), which increases the genetic diversity that may be encountered

Answer 10

- mostly confined to parts of West Central Africa e.g. Gabon

Answer 11

highly divergent from group M and are largely confined to small numbers centred on Cameroon

Answer 12

related to gorilla strains of SIV has been identified from a patient from Cameroon

Answer 13

- at initial exposure, the virus is transported by dendritic cells from mucosal surfaces to regional lymph nodes where permanent infection is established - host cellular receptor that's recognised by HIV surface glycoprotein gp120 is CD4, which defines the cell populations that are susceptible to infection

Answer 14

- interaction between CD4 and HIV gp120 surface glycoprotein - together with host chemokine CCR5 co-receptors - CCR5 CD4 memory T lymphocytes within all body systems are susceptible to infection and depletion; those found in GI tract are heavily infected early in the process and become rapidly depleted leading to compromised mucosal immune function

Answer 15

- co-receptors that work with HIV gp120 glycoprotein and CD4 to allow entry into cells - CCR5 CD4 memory T lymphocytes within all body systems are susceptible to infection and depletion; those found in GI tract are heavily infected early in the process and become rapidly depleted leading to compromised mucosal immune function

Answer 16

- half life of about 6hrs - to maintain observed levels of plasma viraemia, 10^8 to 10^9 virus particles need to be released and cleared daily - virus production by infected cells lasts for about 2 days and is probably limited to death of the cells - HIV replication is linked to the process of CD4 destruction and depletion - loss of activated CD4 T lymphocytes is a key factor in the immunopathogenesis of HIV

Answer 17

- leaves the host open to infections with intracellular pathogens - co-existing antibody abnormalities predispose to infections with capsulated bacteria - associated with a long-term inflammatory state, which is a key driver of disease progression - co-pathogens e.g. cytomegalovirus - translocation of microbial products, e.g. LPS, from the gut into into the systemic circulation following HIV destruction of normal mucosal immunity - raised level of inflammatory cytokines and coagulation system activation - inflammatory responses play a role in HIV-associated end organ damage

Answer 18

- observed from the earliest stages of infection | - leads to an increase in the numbers of susceptible CD4 bearing target cells that can become infected and destroyed

Answer 19

1. binding: virus binds to host CD4 receptor molecules via the envelope glycoprotein gp120 and co-receptors CCR5 and CXCR4 2. fusion: subsequent conformational change results in fusion between gp41 and cell membrane of CD4 3. reverse transcription: entry of viral capsid is followed by uncoating of the RNA. DNA copies are made from both RNA templates. DNA polymerase from host cell leads to formation of dsDNA 4. integration: in nucleus, virally encoded DNA is inserted into the host genome 5. transcription: regulatory proteins control transcription; RNA molecule is synthesised from the DNA template 6. budding: virus is reassembled in the cytoplasm and budded out from the host cell

Answer 20

virus binds to host CD4 receptor molecules via the envelope glycoprotein gp120 and co-receptors CCR5 and CXCR4

Answer 21

subsequent conformational change results in fusion between gp41 and cell membrane of CD4

Answer 22

entry of viral capsid is followed by uncoating of the RNA. DNA copies are made from both RNA templates. DNA polymerase from host cell leads to formation of dsDNA

Answer 23

in nucleus, virally encoded DNA is inserted into the host genome

Answer 24

regulatory proteins control transcription; RNA molecule is synthesised from the DNA template

Answer 25

virus is reassembled in the cytoplasm and budded out from the host cell

Answer 26

by detection of virus-specific antibodies (anti-HIV) or by direct identification of viral material

Answer 27

one which tests for HIV antibody and p24 antigen simultaneously - reduce time between infection and an HIV-positive test result to month; this is several weeks earlier than with sensitive third generation (antibody only detection) assays

Answer 28

- fourth generation ones test for HIV antibody and p24 antigen simultaneously - third generation ones test for antibodies only

Answer 29

- detection of IgG antibody to envelope components - IgG antibody to p24 (anti-p24) - genome detection assays - viral p24 antigen - isolation of virus in culture

Answer 30

- most commonly used - routine tests for screening are based on ELISA techniques, which may be confirmed Western blot assays - up to 3 months may elapse from initial infection to antibody detection (serological window/latency period) - IgG antibodies to HIV have no protective function and persist for life - anti-HIV crosses the placenta - all babies born to HIV-infected women have the anti-HIV antibody at birth

Answer 31

serologic testing algorithm for recent HIV seroconversions - can identify recently acquired infection - a highly sensitive ELISA that detects HIV antibodies 6-8 weeks after infection is used on blood in patients with positive oral fluid test - in parallel with less sensitive test that identifies later HIV antibodies within 130 days - positive result on the sensitive test and negative on the detuned test points to recent infection - positive results on both tests point to infection more than 130 days old

Answer 32

- detected from earliest weeks on infection and through the asymptomatic phase - lost as disease progresses

Answer 33

- nucleic acid-based assays that amplify and test for components of the HIV genome exist - used to aid diagnosis of HIV in babies of HIV infected mothers or where serological tests may be inadequate

Answer 34

- detectable shortly after infection but disappears by 8-10 weeks after exposure - useful marker in individuals who have been infected recently but have not had time to mount an antibody response

Answer 35

specialised technique available in some labs to aid diagnosis and as a research tool

Answer 36

- direct HIV effects - HIV-associated immune dysfunction - drugs used to treat the condition - co-existing morbidity and co-infections

Answer 37

A: asymptomatic or persistant generalised lymphadenopathy or acute seroconversion illness B: HIV related conditions, not A or C C: clinical conditions listed in AIDS surveillance case definition

Answer 38

>500 200-499 <200

Answer 39

A1: >500 CD4 count A2: 200-499 CD4 count A3: <200 CD4 count

Answer 40

B1: >500 CD4 count B2: 200-499 CD4 count B3: <200 CD4 count

Answer 41

C1: >500 CD4 count C2: 200-499 CD4 count C3: <200 CD4 count

Answer 42

USA: includes individuals with CD4 counts below 200 in addition to clinical classification based on presence of specific indicator diagnoses Europe: based on diagnosis of specific clinical conditions with no inclusion of CD4 lymphocyte counts

Answer 43

where HAART is available and started before development of severe immunosuppression

Answer 44

``` candidiasis of bronchi, trachea or lungs candidiasis, oesophageal invasive cervical carcinoma disseminated or extrapulmonary coccidioidomycosis chronic intestinal cryptosporidiosis cytomegalovirus disease CMV retinitis HIV related encephalopathy herpes simplex, chronic ulcers disseminated or extrapulmonary histoplasmosis ```

Answer 45

``` chronic intestinal isosporiasis Kaposi's sarcoma Burkitt's lymphoma immunobasic lymphoma brain lymphoma Mycobacterium avium-intracellulare Mycobacterium TB Pneumocystis jiroveci pneumonia recurrent pneumonia progressive multifocal leucoencephalopathy recurrent Salmonella septicaemia toxoplasmosis of the brain wasting syndrome ```

Answer 46

first 6 month period following HIV acquisition - period of uncontrolled viral replication leading to high levels of HIV circulating in the plasma and genital tract - high infectiousness

Answer 47

2-4 weeks: may be silent both clinically and seologically | - 3-6 weeks: may be a self-limiting nonspecific ilness

Answer 48

- fever - arthralgia - myalgia - lethargy - lymphagenopathy - sore throat - mucosal ulcers - transient faint pink maculopapular rash - headache - photophobia - myelopathy - neuropathy - encephalopathy (rare) lasts up to 3 weeks; recovery usually complete

Answer 49

- lymphopenia with atypical reactive lymphocytes noted on blood film - thrombocytopenia - raised liver transferases - CD4 lymphocytees and the CD4:CD8 ratio is reversed - antibodies to HIV may be absent - circulating viral RNA is high - p24 core protein may be detectable

Answer 50

- rate of clinical progression of untreated HIV is variable - most people with HIV infection are asymptomatic for some time - most people with HIV have a gradual decline in CD4 count over 10 years before progression to AIDS - some progress more rapidly, with continued high levels of viral RNA and a rapid decline in CD4 count over 2-5 years - other long-term non-progressors, may continue with a normal CD4 count over many years

Answer 51

- older age associated with more rapid progression | - women cope less well

Answer 52

- subgroup of patients with asymptomatic infection have this - lymphadenopathy at 2+ extrainguinal sites for more than 3 months in the absence of causes other than HIV infection - nodes are usually symmetrical, firm, mobile and non tender - may be associated splenomegaly - architecture of nodes shows hyperplasia of the follicles and proliferation of the capillary endothelium - nodes may disappear with disease progression - similar disease progression noted in asymptomatic patients with or without PGL

Answer 53

- as HIV infection progresses, the viral load rises, CD4 count falls and patient develops signs and symptoms - clinical picture is result of direct HIV effects and of associated immunosuppression

Answer 54

- microbial exposure of the patient throughout life - pathogenicity of organisms encountered - degree of immunosuppression of the host

Answer 55

- many clinical episodes represent reactivation of previously acquired infection, which has been latent - geographical factors determine the microbial repertoire of individual patients - organisms requiring intact cell-mediated immunity for their control are most likely to cause clinical problems

Answer 56

- high grade pathogens e.g. Mycobacterium tuberculosis, Candida and the herpesviruses are clinically relevant even when immunosuppression is mild, thus occurring earlier in the course of disease - less virulent organisms occur at later stages of immunodeficiency

Answer 57

- when patients are severely immunocompromised (CD4 count <100/mm^3), disseminated infections of organisms of very low virulence e.g. M. avium-intracellulare and Cryptosporidium are able to establish themselves - these infections are very resistant to treatment, because there is no functioning immune response to clear organisms - hierarchy of infection allows for appropriate intervention with prophylactic drugs

Answer 58

- early stage, but clinical neurological involvement increases as HIV advances - AIDS dementia complex (ADC), sensory polyneuropathy and aseptic meningitis - less common since HAART

Answer 59

- release of neurotoxic products by HIV | - cytokine abnormalities secondary to immune dysregulation

Answer 60

- mild memory impairment and poor concentration to severe cognitive deficit, personality change and psychomotor slowing - changes in affect and depressive or psychotic features may be present - spinal cord may show vacuolar myelopathy histologically - atrophic change in severe cases - white matter lesions of increased density on T2 weighted section on MRI - EEG shows non specific changes - CSF normal, protein may be raised

Answer 61

- seen in advanced HIV infection, mainly in the legs and feet, and hands may be affected - severe forms cause intense pain, usually in the feet, which disrupts sleep, impairs mobility and generally reduces quality of life

Answer 62

- may occur with postural hypotension and diarrhoea - autonomic nerve damage in the small bowel - didanosine and stavudine produce similar neuropathy as a toxic side effect

Answer 63

- dry skin and scalp - onychomycosis - seborrhoeic dermatitis - tinea: cruris and pedis - pityriasis: versicolor and rosea - folliculitis - acne - molluscum contagiosum - warts - herpes zoster: multidermatomal and disseminated - papular pruitic eruption - scabies - ichthyosis - Kaposi's sarcoma

Answer 64

- candidiasis: oral and vulvovaginal - oral hairy leucoplakia - aphthous ulcers - herpes simplex: genital, oral, labial - periodontal disease - warts: oral and genital

Answer 65

- eye pathology seen in later stages - cytomegalovirus retinits: sight-threatening - retinal cotton wool spots - anterior uveitis: present as acute red eye associated with rifabutin therapy for mycobacterial infections in HIV - pneumocystis, toxoplasmosis, syphilis and lymphoma can affect the eye/retina

Answer 66

- function of dendritic and Langerhans' cells, both target cells for HIV, are disrupted - delayed-type hypersensitivity is reduced or absent even before clinical signs of immunosuppression appear

Answer 67

common in advanced HIV infection - lymphopenia progresses as the CD4 count falls - anaemia of chronic HIV infection is usually mild, normochromic and normocytic - neutropenia is common and usually mild - isolated thrombocytopenia - pancytopenia: occurs due to underlying opportunistic infection or malignancies

Answer 68

- may occur early in infection and be only manifestation of HIV for some time - platelet counts are moderately reduced - circulating antiplatelet antibodies lead to peripheral destruction - megakaryocytes are increased in bone marrow but their function impaired - effective antiretroviral therapy usually increases platelet count - thrombocytopenic patients undergoing dental, medical or surgical procedures may need therapy with human immunoglobin, which increases platelet count, or given transfusion - steroids should be avoided

Answer 69

- zidovudine (megaloblastic anaemia, red cell aplasia, neutropenia) - lamivudine (anaemia, neutropenia) - ganciclovir (neutropenia) - systemic chemotherapy (pancytopenia) - co-trimoxazole (agranulocytosis)

Answer 70

- weight loss and diarrhoea - wasting in advanced infection is usually due to anorexia - small increase in resting energy expenditure, but weight and lean body mass usually remain normal in periods of clinical latency - GI infections are ocmmon - villous atrophy with chronic diarrhoea - hypochlorhydria in advanced disease - rectal lymphoid tissue cells may be resevoirs for infection

Answer 71

- HIV-associated nephropathy (HIVAN) - nephrotic syndrome - nephrotoxic drugs used for HIV

Answer 72

HIV-associated nephropathy - rare - causes significant renal impairment, esp. in advanced disease - most frequently seen in black males - can be exacerbated by heroin use

Answer 73

- subsequent to focal glomerulosclerosis - consequence of HIV cytopathic effects on renal tubular epithelium - course is usually relentless; dialysis may be needed

Answer 74

- foscarnet - amphotericin B - pentamidine - sulfadiazine - tenofovir

Answer 75

- upper airways and lungs are a physical barrier to air-borne pathogens - damage decreases efficiency of protection, leading to an increase in upper and lower respiratory tract infections - sinus mucosa may function abnormally, and is a frequent site of chronic inflammation - lymphoid interstitial pneumonitis (LIP): paediatric HIV infection

Answer 76

lymphoid interstitial pneumonitis - well described in paediatric HIV infection, uncommon in adults - infiltration of lymphocytes, plasma cells and lymphoblasts in alveolar tissue - Epstein-Barr virus may be present - dyspnoea and dry cough - reticular nodular shadowing on chest x-ray - therapy with steroids

Answer 77

- reduced testosterone and abnormal adrenal function - intercurrent infection superimposed upon borderline adrenal function precipitates clear adrenal sufficiency, requiring replacement doses of gluco- and mineralocorticoid

Answer 78

- lipid dysregulation associated with antiretroviral medication - HDL levels are lower in those with untreated HIV than in HIV-negative controls - ischaemic heart disease more common in intermittent ARV therapy than those who maintained viral suppression - cardiomyopathy (rare) may lead to congestive cardiac failure - lymphocytic and necrotic mycocarditis

Answer 79

- defective T cell function against protozoa, fungi and viruses - impaired macrophage function against intracellular bacteria - defective B-cell immunity against capsulated bacteria

Answer 80

``` Toxoplasma gondii Cryptosporidium parvum Microsporidia spp. Leishmania donovani Isospora belli ```

Answer 81

``` Cytomegalovirus Herpes simplex Varicella Zoster Human papillomavirus JC polyoma virus ```

Answer 82

``` Pneumocystis jiroveci Cryptococcus neoformans Candida spp. Dermatophytes (Trichophyton) Aspergillus fumigatus Histoplasma capsulatum Coccidiodes immitis ```

Answer 83

``` Salmonella spp. Mycobacterium tuberculosis M. avium-intracellulare Streptococcus pneumoniae Staphylococcus aureus Haemophilus influenzae Moraxella catarrhalis Rhodococcus equii Bartonella quintana Nocardia ```

Answer 84

- newly diagnosed patients should be reviewed by an HIV clinician within 2 weeks of diagnosis - earlier if they're symptomatic or has acute needs - full medical history, physical examination and lab evaluation should be done to determine stage of infection, presence of co-morbidities and co-infections and to assess overall physical, mental and sexual health - details of socioeconomic situation, relationships, family and social support networks and substance misuse

Answer 85

regularly (approx. every 3 months) to assess progression of infection and need for treatment

Answer 86

- CD4 lymphocyte counts - patients below 200 cells are at greatest risk for HIV-related pathology - rapidly falling CD4 counts and those below 350 are indications for HAART - factors other than HIV (smoking, exercise, intercurrent infections and diluminal variation) affect CD4 counts - CD4 counts are done every 3 months or more if critical levels are being approached

Answer 87

FBC, differential count and film

Answer 88

- serum, liver and renal function including eGFR - fasting serum lipid profile, total cholesterol, HDL cholesterol - fasting blood glucose - serum bone profile including 25 OH vitamin D - urinalysis - dipstick for blood, protein and glucose - urine protein/creatinine ratio

Answer 89

- lymphocyte subsets | - HLA B*5701 status

Answer 90

- HIV antibody - HIV viral load - HIV genotype and subtype determination - HepA IgG - HepB surface antigen and full profile - HepC antibody

Answer 91

- toxoplasmosis serology - syphillis serology - screen for other STIs

Answer 92

- cervical cytology - chest x-ray if indicated - 10 year cardiovascular risk assessment - fracture risk assessment

Answer 93

- HIV replicates at a high rate throughout the course of infection - many billion new virus particles produced daily - rate of viral clearance is constant and level of viraemia is a reflection of the rate of virus replication; this has prognostic and therapeutic value

Answer 94

viral load encompasses viraemia and HIV RNA levels - branched-chain DNA (bDNA) - reverse transcription polymerase chain reaction (RT-PCR) - nucleic acid sequence based amplification (NASBA)

Answer 95

- results of assays are given in copies of viral RNA/mL of plasma, or converted to a logarithmic scale - good correlation between tests - transient increases in viral load are seen after immunisations or in acute intercurrent infection - by 6 months after seroconversion to HIV, the viral set point for an individual is established - correlation between HIV RNA levels and long-term prognosis, independent of CD4 count

Answer 96

- clear genotype variations exist within HIV - between viral subtypes and also with well-identified point mutations associated with resistance to antiretroviral drugs - most appropriate sample for this is one closest to the time of diagnosis and results are used to guide selection of HAART agents

Answer 97

- inability of current drugs to clear HIV from certain intracellular pools - adherence requirements - complex drug-drug interactions - emergence of resistant viral strains

Answer 98

- maintain physical and mental health - improve quality of life - increase survival rates - restore and improve immune function - avoid onward transmission - provide appropriative palliative support as needed

Answer 99

period in which HIV antibodies first become detectable

Answer 100

- sharp increase and then decrease in viral load, becoming low and staying there at 4-6 weeks - sharp increase in antibody to gp120 and CD4 cells, then relative plateau - antibody to gp120 increases more than CD4 cell count

Answer 101

- plateau/small increase in viral load - small increase then decrease in CD4 cells - increase then plateau of antibody to gp120

Answer 102

- increase in viral load - decrease in CD4 cells - plateau/small decrease in antibody to gp120

Answer 103

- sharp decrease in viral load - increase in CD4 cells - decrease in antibody to gp120

Answer 104

- long term maximal suppression of HIV activity using antiretroviral medication and MDT management - regular assessment for details of intercurrent medical problems, medications, vaccinations, drug use, sexual history, reproduction, cervical cytology, social situation, employment, benefits and accommodiation - mood and cognitive function should be routinely assessed - psychological support for patient and family - sexual and reproductive health and advice - monitoring of weight, BMI, BP and cardiovascular risk - dietary assessment and advice - general health protection advice

Answer 105

- ADRs - acute opportunistic infections - presentation or complication of malignancy - immune reconstitution phenomenon - infection in an immunocompromised host - organic or functional brain disorders - non-HIV related pathology must not be forgotten

Answer 106

- ART, prophylaxis, travel, previous HIV-related pathology, potential source of infectious agents (food hygeine, pets, contacts with acute infections, contact with TB, STIs) - secure confidentiality

Answer 107

- signs of ADRs - signs of disseminated sepsis - clinical evidence of immunosuppression - focal neurological signs and/or meningism - evidence of altered mental state - organic or function - examine: genitalia, fungi, mouth - lymphadenopathy

Answer 108

- FBC and differential count - liver and renal function tests - plasma glucose - blood gases including acid-base balance - blood cultures - microscopy and culture of available/appropriate specimens: stool, sputum, urine, CSF - malaria - serological tests fro cryptococcal antigen, toxoplasmosiss - chest x-ray - CT/MR scan of brain in focal neurological signs and always before lumbar puncture

Answer 109

- increased potency - reduced toxicity - greater convenience of formulation - compounds with different mechanisms of action - improved understanding of drug resistance

Answer 110

- reverse transcriptase inhibitors - protease inhibitors - integrase inhibitors - fusion inhibitors - co-receptor blockers

Answer 111

- nucleoside/nucleotide analogues | - non-nucleoside analogues

Answer 112

- NRTIs inhibit the synthesis of DNA by reverse transcription and also act as DNA chain terminators - NRTIs need to be phosphorylated intracellularly for activity to occur - two drugs of this class are combined to provide the backbone of a HAART regimen - NRTIs are associated with mitochondrial toxicity, due to effects on mitochondrial DNA polymerase - lactic acidosis is a complication - nucleotide analogues have a similar mechanism of action but require 2 intracellular phosphorylation steps (3 for nucleoside analouges)

Answer 113

- NNRTIs interfere with reverse transcriptase by direct binding to the enzyme - they're small molecules that are widely disseminated throughout the body and have a long half-life - affect cytochrome P450 - ineffective against HIV-2 - level of cross-resistance across the class is high - all associated with rashes and elevation of liver enzymes - second-generation NNRTIs, e.g. etravirine and rilpivirine,

Answer 114

- act competitively on the HIV aspartyl protease enzyme, which is involved in the production of functional viral proteins and enzymes - viral maturation is impaired and immature dysfuntional viral proteins are produced - most protease inhibitors are active at low conc. and in vitro are found to have synergy with reverse transcriptase inhibitors - cross-resistance can occur across group - no activity against human aspartyl proteases, but there are interactions with cytochrome P450 - abnormalities of fat metabolism and control of blood sugar - deterioration in clotting function

Answer 115

- act as a selective inhibitor of HIV integrase, which blocks viral replication by preventing insertion of HIV DNA into the human genome - raltegravir is metabolised by glucuronidation and does not require retroviral drug boosting - effective in treating experienced and naive patients

Answer 116

- maraviroc is a chemokine receptor antagonist - blocks cellular CCR5 receptor by CCR5 tropic strains of HIV - strains are found in earlier HIV infection and with time adaptations they allow the CXCR4 receptor to become the more dominant form - drug is metabolised by CYP p450 (3A), giving potential drug interactions - tropism assays to establish that the patient is carrying a CCR5 tropic virus are required

Answer 117

- enfurvitide - injectible peptide derived from HIV gp41 that inhibits gp41-mediated fusion of HIV with the target cell - synergistic with NRTIs and PIs - no evidence of cross-resistance with other drug classes - has an extracellular mode of action - few interactions - side effects related to subcutaneous route of administration

Answer 118

tenofovir, abacavir, zidovudine, stavudine, lamivudine, emtricitabine

Answer 119

efavirenz, nevirapine, etravirine

Answer 120

raltegravir

Answer 121

fosamprenavir, atazanavir, darunavir, lopinavir, saquinavir

Answer 122

enfuvitide

Answer 123

- must be taken exactly as prescribed - should not be stopped suddenly - can be compromised by the introduction of other medications, including other ARVs and vice versa - can adversely interact with some herbal, complementary and recreational agents - may produce additive toxicities when given with other medications - are associated with a range of adverse drug reactions which may be confused with other pathology - may exacerbate co-morbidities

Answer 124

- symptomatic HIV disease - AIDS - CD4 count consistently below 200 cells mm^3 significant risk of serious HIV-associated morbidity and mortality and the longer-term prognosis for patients initiating therapy below 200 CD4 cells/mm^3 is not as good

Answer 125

- around 350 should start | - 200 to 350 should start as soon as possible

Answer 126

500 cells/mm^3 or above

Answer 127

> 60000 copies/mL

Answer 128

losing more than 80 cells/year

Answer 129

two NRTIs in combination, with either an NNRTI or a boosted protease inhibitor - development of fixed-dose coformulations reduces pill burden, increases convenience and facilitates adherence

Answer 130

- which two NRTIs form the backbone is influenced by efficacy, toxicity and ease of administration - availability of OD one-tablet fixed dose combinations, Truvada (TDF/FTC) and Kivexa (ABC/3TC), has led to most patients being prescribed one of these - Combivir (ZDV/3TC) is a twice-daily dosing schedule and has lower efficacy and poorer toxicity profile

Answer 131

Truvada (TDF/FTC) | Kivexa (ABC/3TC)

Answer 132

- once daily one tablet fixed dose combination of NRTIs used in HAART - TDF/FTC

Answer 133

- once daily one tablet fixed dose combinations of NRTIs used in HAART - ABC/3TC - only used in those who are HLAB*5701

Answer 134

- twice daily dosing schedule and poorer toxicity profile than Truvada - ZDV/3TC

Answer 135

- associated with lipodystrophy and peripheral neuropathy and is no longer used as a first-line therapy in the UK - used in other parts of the world

Answer 136

- efavirenz - nevirapine - etravirine and rilpivirine

Answer 137

- NNRTI used in HAART - recommended option in the UK - good durability over time, potency at low CD4 counts and in high viral loads - once-daily dosing - associated with CNS side-effects e.g. dysphoria and insomnia and is contraindicated in pregnancy - fixed-dose preparation of efavirenz co-formulated with Truvada (Atripla) allows for a one pill once a day regimen

Answer 138

- NNRTI used in HAART - equivalent potency to efavirenz but has a higher incidence of hepatoxicity and rash - toxicity is greater in women and in those with higher CD4 counts - contraindicated in women with CD4 counts above 250 cells and in men with counts above 400 - useful alternative to efavirenz if CNS side-effecs are troublesome and in women with lower CD4 counts who wish to conceive

Answer 139

- second generation NNRTIs - used in HAART - active against drug-resistant strains and useful in treatment of experienced patients

Answer 140

- used with two NRTIs - excellent efficacy in clinical practice - usually combined with a low dose of ritonavir which blocks cytochrome P450 metabolism - half-life of the active drug is increased, allowing greater drug exposure, fewer pills, enhanced potency and reduced risk of resistance - greater pill burden and increased risk of lipid abnormalities, raised fasting TGs

Answer 141

- atazanavir, darunavir or lopinavir, boosted with ritonavir are most commonly used as first line therapy - all three can cause GI disturbance and lipid abnormalities - atazanavir increases unconjugated bilirubin levels and may produce icterus - all have interactions with cytochrome P450

Answer 142

- treatment in clinical trial - neurological involvement - if the CD4 <200 for > months - if an AIDS-defining illness is present

Answer 143

CD4 <250 treat CD4 251-350 treat ASAP CD4 >350 consider enrolment into when to start trial AIDS diagnosis/CDC stage C - treat (except for TB when CD4 >350)

Answer 144

- tenofovir | - emtricitabine

Answer 145

- atazanavir/ritonavir - darunavir/ritonavir - efavirenz - raltegravir

Answer 146

- abacavir | - lamivudine

Answer 147

- lopinavir/ritonavir - fosamprenavir/ritonavir - nevirapine - rilpiverine

Answer 148

- by 4 weeks of therapy, the viral load should have dropped by at least 1 log10 copies/mL and by 12-24 weeks should be below 50 copies/mL - suboptimal response at either time point demands a full assessment and possible change in therapy

Answer 149

- viral load should be routinely measured every 3-4 months - CD4 count should be repeated at 1 and 3 months after starting HAART and then every 3-4 months - once the viral load is below 50 copies/mL and the CD4 count has been above 350 cells for 12 months frequency may fall to 6 monthly

Answer 150

- review of adherence to and tolerability of the regimen, weight, blood pressure adn urinalysis - monitored for drug toxicity, including FBC, liver and renal function and fasting lipids and gluose levels

Answer 151

- assessment of adherence to medication | - evidence of ART toxicity

Answer 152

- BP - weight - HIV viral load - lymphocyte subsets - FBC - urinalysis if taking tenofovir - liver and renal function - fasting lipid profile - fasting blood glucose

Answer 153

- HIV genotype if there is evidence of virological failure | - therapeutic drug level monitoring

Answer 154

1. HIV replicates rapidly and inaccurately; replication in presence of ART leads to selection pressure for mutations which can survive 2. specific point mutations in the viral reverse transcriptase protease and integrase genes correlate with reduced drug sensitivity 3. inadequate ARV drug levels fail to suppress viral replication/viral load and percipitate drug resistance 4. inadequate drug levels 5. some ARVs have a low genetic barrier 6. stopping drugs with a long half-life can leave a subtherapeutic drug tail for long enough for resistant strains to develop 7. therapeutic drug monitoring 8. introduction of new drugs can impact cytochrome P450 9. wild type virus reasserts itself without drug selection pressure 10. resistant variants survive and are archived. reappear if selection pressure is reintroduced.

Answer 155

selection pressure for those that can survive

Answer 156

- poor adherence, altered GI tract absorption, increased drug breakdown and drug-drug interactions - fail to suppress viral replication/viral load and precipitate drug resistance

Answer 157

small number of mutations that occur rapidly can quickly result in high levels of resistance

Answer 158

- leave a subtherapeutic drug tail for long enough for resistant strains to develop

Answer 159

wild type virus reasserts itself and resistant variants no longer make up the major circulating viral strains and may not be found on investigation - genotyping should be done

Answer 160

- survive and are archived - reappear if drug selection pressure is reintroduced - all previous genotypes need to be considered when assessing virological failure and planning new therapy

Answer 161

- side-effects of medications - degree of complexity and pill burden - inconvenience of the regimen - level of motivation and commitment to the therapy - psychological wellbeing - level of available family and social support and health beliefs

Answer 162

- patients beliefs about their personal need for medicines and their concerns about treatment affect how or whether they take them - levels of adherence below 95% have been associated with poor virological and immunological responses - poor absorption and low bioavailability leads to levels being inadequate to suppress viral replication - even missing a single dose will reduce plasma drug levels a lot - patchy adherence facilitates emergence of drug-resistant variants, which lead to virological treatment failure

Answer 163

- persistent viral replication causing immunological deterioration and eventual clinical evidence of disease progression - caused by poor adherence, limited drug potency, substances that compromise drug absorption, interaction, limited penetration, side effects etc

Answer 164

- rise in viral load - falling CD4 count - new clinical events that imply progression of HIV disease

Answer 165

two consecutive viral loads of >400 copies/mL in a previously fully suppressed patient

Answer 166

- cumulative toxicity - potential drug interactions with medications - poor adherence (stopping completely is preferable to continuing with inadequate dosing, to reduce the development of viral resistance) - poor quality of life - views of the patient

Answer 167

- abacavir is associated with a potentially fatal hypersensitivity reaction, associated with the presence of HLAB*5701, usually in first 6 weeks - may be a discrete rash and fever, malaise and GI/resp symptoms - rechallenge with abacavir can be fatal and is contraindicated - allergies to NNRTIs (second or third week of treatment) present with widespread maculopapular pruritic rash with fever and disordered liver biochemical tests - drugs should be stopped in mucous membrane involvement or severe hepatic dysfunction

Answer 168

- characteristic morphological changes and metabolic abnormalities - loss of subcutaneous fat in the arms, legs and face, deposition of visceral, breast and local fat, raised total cholesterol, HDL cholesterol and triglycerides and insulin resistance with hyperglycaemia - associated with increased cardiovascular morbidity - PIs and NRTIs have been implicated - statins and fibrates recommended, and tesamorelin

Answer 169

- mitochondrial toxicity involes stavudine and didanoside (nucleoside analogues) and leads to raised lactate and lactic acidosis - NRTIs inhibit gamma DNA polymerase and other enzymes necessary for mitochondrial function - symptoms include anorexia, nausea, abdominal pain and general malaise - venous lactate is raised and the anion gap is widened - requires immediate cessation of ART and supportive measures until normal biochemistry is restored

Answer 170

- bone disorders are reported in HIV, e.g. osteoporosis, osteopenia and avascular necrosis - varied prevalence - ARVs, esp. PIs, have been implicated in the aetiology

Answer 171

immune reconstitution inflammatory syndrome - occurs in people who have been very immunosuppressed and begin therapy - as their immune system recovers, they can mount an inflammatory response, which can exacerbate symptoms - unusual mass lesions or lymphadenopathy associated with mycobacteria, deteriorating radiological appearances associated with TB - inflammatory retinal lesions in association with cytomegalovirus, deterioration in liver function in chronic hep B carriers and vesicular eruptions with herpes zoster

Answer 172

- allergic reactions - lipodystrophy and metabolic syndrome - mitochondrial toxicity and lactic acidosis - bone metabolism - IRIS

Answer 173

- unique opportunity for therapy as there's less viral diversity and the host immune capacity is still intact - viral load can be reduced substantially by aggressive therapy at this stage, but it rises when treatment is withdrawn - people with severe symptoms during primary HIV infection may gain a clinical improvement on ARVs

Answer 174

- in the UK, the mother-to-child HIV transmission rate is 1% for all women diagnosed prior to delivery and 0.1% for women on HAART with a viral load below 50 copies/mL - management aim is to deliver a healthy, uninfected baby to a healthy mother without prejudicing future treatment options of the mother - breastfeeding doubles the risk of vertical transmission - triple therapy is used - risk of vertical transmission increases with viral load - treatment should start ASAP and continue during delivery

Answer 175

post-exposure prophylaxis - animal models provide support for use of triple ARVs - healthcare workers and those exposed sexually can be given this - risk of acquisition of HIV following exposure is dependent upon the risk that the source is HIV positive and the risk of transmission of the exposure - may be useful up to 72 hours after exposure - in the UK, the standard regimen is Truvada plus Kaletra - given for 4 week - toxicity should be monitored

Answer 176

- pneumocystis jiroveci - non-TB mycobacterial species - Nocardia spp - Aspergillus spp - Zygomycetes spp - Penicillium spp - Cryptococcus spp. - Histoplasma capsulatum - Coccidomycosis - Paracoccidiodomycosis - Blastomycosis - CMV - respiratory syncyitial virus - toxoplasma gondii

Answer 177

impaired cell-mediated immunity; HIV infection with CD4 < 200/mm^3, long-term corticosteroid use, immunosuppressant drugs

Answer 178

- pneumocystis pneumonia | - perihilar ground-glass shadowing, cysts

Answer 179

impaired cell-mediated immunity; HIV infection CD4 usually < 200mm^3 structural lung disease: bronchiectasis, CF, severe COPD

Answer 180

- varied clinical presentation: non-specific fevers, cough, malaise, lymphadenopathy, hepatosplenomegaly - CT findings: nodules, cavitation, thickened airways, tree in bud small airways

Answer 181

impaired cell-mediated immunity: HIV infection CD4 usually <150/mm^3, chronic corticosteroid use, post-solid-organ transplantation, post stem cell transplantation structural lung disease: bronchiectasis, CF, severe COPD

Answer 182

- acute sub-acute or chronic pneumonia | - multiple radiographic presentations: lobar infiltrates, abscesses, cavities, pleural effusion, pulmonary nodules

Answer 183

prolonged neutropenia: post-chemotherapy for haematological malignancy, post-stem cell transplant impaired cell-mediated immunity: graft-versus-host disease, immunosuppressant therapy chronic granulomatous disease

Answer 184

- invasive fungal pneumonia characterised by cough, haemoptysis, pleuritic pain and fevers - CT findings: cavitating consolidation, tree in bud, nodules with ground glass halo and in later stages air-crescent sign (caused by lung necrosis)

Answer 185

impaired cell-mediated immunity: HIV infection CD4 usually <200/mm^3, chronic corticosteroid use, post-solid-organ transplantation, post-stem cell transplantation

Answer 186

- nonspecific respiratory symptoms of fever, cough, breathlessness - usually associated with neurological involvement, isolated pulmonary disease does occur - progresses to disseminated disease in immunocompromised patients - CT findings: cavitites, nodules, infiltrates

Answer 187

impaired cell-mediated immunity: HIV infection CD4 usually <50/mm^3

Answer 188

- fever, fatigue, weight loss - cough and dyspnoea are most common respiratory symptoms - chest x-ray can be normal in disseminated disease - CT findings: diffuse reticular/reticulonodular infiltrates, miliary infiltrates, occasionally mediastinal lymphadenopathy

Answer 189

impaired cell-mediated immunity: HIV infection CD4 usually <50/mm^3

Answer 190

- often presents as disseminated disease (chext x-ray often normal) - focal or diffuse pneumonia - CT findings: diffuse reticulonodular infiltrates, consolidation, nodules, cavities, mediastinal lymphadenopathy

Answer 191

impaired cell-mediated immunity: HIV infection CD4 usually <50/mm^3, post-transplantation on immunosuppressant therapy

Answer 192

- cough dyspnoea and fever | - CT findings: reticular or ground-glass opacities, alveolar infiltrates, nodules/nodular opacities, pleural effusions

Answer 193

impaired cell-mediated immunity: HIV infection CD4 usually <200/mm^3, chronic corticosteroid use, post-solid-organ transplantation, post-stem cell transplantation

Answer 194

- cough dyspnoea and fever | - CT findings: ground glass opacification, air-space shadowing, tree in bud, airway dilation and wall thickening

Answer 195

impaired cell-mediated immunity: HIV infection CD4 usually <100/mm^3

Answer 196

- isolated pulmonary or disseminated disease - dry cough, fever, dyspnoea - CT findings: appearance similar to PCP or fungal pneumonia; pleural effusion

Answer 197

``` anthrax cholera- WC/rBS hepatitis A and B haemophilus influenzae b influenza - parenteral Japanese encephalitis meningococcus - MenC, ACWY, PPV23 poliomyelitis - parenteral (IPV) rabies tetanus-diphtheria tick-borne encephalitis typhoid - ViCPS ```

Answer 198

``` cholera - CVD103-HgR (live) influenza - intranasal (live) poliomyelitis - oral (OPV) (live) typhoid - Ty21a (live) TB (BCG) (live) smallpox (vaccinia) (live) ```

Answer 199

measles, mumps, rubella (MMR) varicella yellow fever

Answer 200

- avoid infection - immunisation strategies - chemoprophylaxis

Answer 201

- food and hygeine - reduce exposure to Salmonella, toxoplasmosis and Cryptosporidium and protected sexual intercourse will reduce exposure to herpes simplex virus, hepatitis B and C and papillomavirus - CMV-negative patients should be given CMV-negative blood products - travel-related infection can be minimised with appropriate advice

Answer 202

- many OIs are hard to eradicate using antimicrobials and the recurrence rate is high - primary and secondary prophylaxis have reduced incidence of many OIs

Answer 203

potential for toxicity, drug interactions and cost

Answer 204

- effective in reducing the risk of Pneumocystis jiroveci, toxoplasmosis and Mycobacterium avium-intracellulare - not normally recommended against CMV, herpes viruses or fungi

Answer 205

- high CD4 count (1050 cells/mm^3) | - low HIV/RNA copies (10^2 per ml plasma)

Answer 206

- decrease to 500 CD4 count per mm^3 at 6 weeks, then increase to about 600 - sharp increase in HIV RNA copies, to a peak of about 10^6 per ml plasma at 6 weeks, then a sharp decrease to 10^3.5

Answer 207

- rise of CD4 count to 700 cells per mm^3 at 12 weeks, then decrease until about 8 years - slow increase in HIV RNA copies from 10^3.5 at 9 weeks to 10^4 at 8 years

Answer 208

- slow increase of HIV RNA copies, about 10^4 per ml plasma | - decreasing CD4 count

Answer 209

- increase in HIV RNA copies, 10^5 when OIs occur and around 10^6.5 at death - CD4 counts very low, around 50 when OIs occur and 10 at death

Answer 210

- CD4 cell count | - HIV viral load

Answer 211

- seroconversion - usually within 2-4 weeks of infection - similar to glandular fever/flu

Answer 212

- fever - sore throat - myalgia - rash - vomiting and diarrhoea - headache - lymphadenopathy - weight loss if symptoms are more severe, their disease will progress more rapidly

Answer 213

- ask about sexual history | - think of HIV seroconversion

Answer 214

- undiagnosed - immune system starts to take control and the CD4 cell population increases, and the viral load decreases - over time the CD4 population slowly declines until the person is immunosuppressed enough to present with constitutional symptoms and OIs - 8 years

Answer 215

- no symptoms | - may notice some enlarged lymph nodes -> persistent generalised lymphadenopathy

Answer 216

enlarged lymph nodes involving at least 2 areas of the body for at least 3 months

Answer 217

- bacterial - viral - fungal - autoimmune - constitutional

Answer 218

- pelvic inflammatory disease - listeriosis - recurrent sinusitis - bacterial pneumonia

Answer 219

- oral hairy leucoplakia - shingles - cervical dysplasia CIN - peripheral neuropathy - molluscum contagiosum - herpes simplex

Answer 220

- oral or vaginal candida (thrush) - fungal nail - tinea capitis - seborrhoeic dermatitis

Answer 221

- chronic diarrhoea - pyrexia of unknown origin - weight loss - lymphadenopathy

Answer 222

when faced with a common problem in: - an unexpected patient - no clear underlying cause - recurring infections

Answer 223

acquired immune deficiency syndrome - CD4 <200 - AIDS defining illness present

Answer 224

pneumocystis pneumonia (PCP) - fungal pneumonia (Pneumocystis jirovecii) - 42.6% prevalence in AIDS

Answer 225

fevers, SOB, dry cough, pleuritic chest pain, exertional drop in oxygen sats

Answer 226

chest xray - can be normal - if abnormal, variable - classically bilateral interstitial changes in perihilar areas ABG for hypoxia induced sputum for PCR - nebulised saline to acquire sputum

Answer 227

co-trimoxazole (trimethoprim + sulfamethoxazole) | - +/- prednisolone (steroids) if hypoxic

Answer 228

pneumocystis pneumonia

Answer 229

- increased transmission - increased morbidity - increased mortality

Answer 230

- streptococcus pneumonia - haemophilus influenzae - s. aureus - pseudomonas aeruginosa - escherichia coli - mycobacterium TB - non-TB mycobacterium

Answer 231

- pneumocysitis jirovecii (PCP) - candidiasis - aspergillus spp - cryptococcus neoformans - histoplasmosis - penicillium marneffei - coccidioidomycosis

Answer 232

- CMV pneumonitis - adenovirus - herpes simplex pneumonitis

Answer 233

- stronglyoids stercoralis | - toxoplasma gondii

Answer 234

- Kaposi's sarcoma - lymphoma - lung cancer - immune reconstitution inflammatory syndromes (IRIS) - emphysema - pulmonary hypertension - interstitial pneumonitis

Answer 235

mass lesions - primary CNS lymphoma - M. TB - toxoplasmosis opthalamic - toxoplasmosis - m. TB - CMV meningitis - m. TB - pneumococcal meningitis - cryptococcal meningitis

Answer 236

- single mass with surrounding oedema | - lymphocytic CSF

Answer 237

- reactivation of latent infection - seroprevalence 15-50% - CD4 <100 - bilateral ring enhancing lesions on MRI - treated with sulphadiazine and pyrimethamine (+ folic acid)

Answer 238

- reactivation of latent infection - up to half of the UK population will have the infection at some point - IgG negative -> IgG positive - CD4 <100 - bilateral ring enhancing lesions on MRI - treated with sulphadiazine and pyrimethamine (+folic acid)

Answer 239

- ocular TB can involve any part of the eye (e.g. uveitis, retinal, orbit, external eye) and can occur with or without evidence of systemic TB - picture is choroidal granuloma - histology: granulomas and AFBs - develops following hematogenous spread from a primary focus, but in rare cases can also occur as a primary infection following an epithelial injury

Answer 240

(val)ganciclovir

Answer 241

- variable presentation as an acute meningitis to a progressive dementia - cranial nerve palsies (most often 6th) - insidious onset of headache: 1 day to 6 months - night sweats and fevers - vomiting - active pulmonary TB present in 30-60% of cases - without treatment, proceeds to coma and death

Answer 242

- neurophil polymorphs - high protein - low glucose

Answer 243

- lymphocytes on microscopy - high protein - variable glucose

Answer 244

- lymphocytes on microscopy - high protein - low glucose

Answer 245

- caused by strep pneumoniae - common pathogen in immunocompetent meningitis too - associated with neurological sequelae - patients are immunised against strep pneumo

Answer 246

- gradual onset headache and fever (weeks) - little to find on examination and CT - very high opening pressure - india ink stain to visualise on microscopy - treat with amphoteracin B and flucytosine

Answer 247

increases risk of any cancer that's associated with a virus - human herpes virus 8 -> Kaposi's sarcoma - epstein barr virus -> lymphomas - human papillomavirus -> cervical, anal, penile carcinoma - hepatitis B/C -> hepatocellular carcinoma - anal cancer - seminoma - head and neck cancer - Castleman's disease - vaginal neoplasia - penile cancer

Answer 248

- caused by human herpesvirus 8 - usually associated with HIV - single -> multiple lesions - usually on the skin - rarely genetic - other sites: mouth, GI tract -> GI bleed, respiratory tract - treated with HAART and chemo/radiotherapy

Answer 249

``` cerebral toxoplasmosis* TB* primary CNS lymphoma* cryptococcal meningitis* CMV retinitis* progressive multifocal leukoencephalopathy (JC virus)* HIV encephalopathy* viral encephalitis (HSV, CMV*, VZV) ```

Answer 250

``` persistent HSV* Kaposi's sarcoma* shingles (VZV) molluscum contagiosum fungal skin infections severe psoriasis ```

Answer 251

wasting syndrome* recurrent salmonella sepsis* cervical cancer* other viral associated cancers

Answer 252

``` recurrent pneumonia* PCP* TB* Kaposi's sarcoma* candidiasis* CMV or HSV pneumonitis* lymphoma* histoplasmosis* coccidiomycosis* aspergillus ```

Answer 253

``` Kaposi's sarcoma* CMV colititis* candidiasis* (oral candida isn't AIDS defining) HSV oesophagitis* cryptosporidium* isosporiasis* disseminated MAI* ```

Answer 254

- 1 mutation in every 2 new viruses - 1-10 billion new virus particles each day - 1-5 billion mutations per day

Answer 255

1. non adherence | 2. drug-drug interactions

Answer 256

1. CD4 and viral load are used to monitor infection 2. in a patient with fever, rash and non-specific symptoms - ask about sexual history/risks and think of HIV seroconversion 3. think about doing a HIV test when faced with a common problem in an unexpected patient/no reason for symptoms/recurring infection 4. PCP is the most common opportunistic infection 5. consider a lumbar puncture in a seropositive person with a headache 6. with current HAART regimes, PLWH can live a normal life 7. good adherence and avoidance of drug interactions are key to avoid drug resistance

Answer 257

- people living with HIV: 37.9 million - people newly infected with HIV: 1.7 million - HIV related deaths: 770000 - about 5000 new infections (adults and children) a day - 61% in sub-Saharan Africa - 500 are among children under 15 - number of PLWH has steadily increased from 1990s - number of deaths in adults and children increased from 1990 and peaked in 2005, then has gradually decreased

Answer 258

90/90/90 global target - 90% of people living with HIV being diagnosed - 90% diagnosed on ART - 90% viral suppression for those on ART by 2020 - 30 million people on treatment - fewer than 500000 new HIV infections annually

Answer 259

- latest MPES estimates showed the number of PLWH as 103800 | - estimated 7500 of these people living with an undiagnosed infection

Answer 260

- diverse group | - assumptions about the characteristics of those living with HIV should be challenged

Answer 261

- blood - sexual - vertical

Answer 262

- ARV treatment (U=U) - PreP - circumcision - PEP - STI control - vaccines - microbicides - HIV diagnosis/partner notification - behavioural/condom use - screen blood products/needle exchange

Answer 263

undetectable = untransmittable - review produced 4000 couple-years of follow up - combined HIV transmission risk estimate while HIV positive person was virally suppressed, of 0.00 (0.00-0.07) per 100 couple years - no cases of linked HIV transmission to sexual partners when the person with HIV was virally suppressed have been documented

Answer 264

pre-exposure prophylaxis - when people at risk for HIV take daily medicine to prevent HIV - can stop HIV from spreading through the body - when taken daily, it's highly effective for preventing HIV from sex or injection drug use - less effective when not taken consistently

Answer 265

post exposure prophylaxis - taking ART after being potentially exposed to HIV to prevent becoming infected - used only in emergency situations - must be started within 72 hours after a recent possible exposure to HIV

Answer 266

- receptive anal intercourse (0.1-3%) - receptive vaginal intercourse (0.1-0.2%) - insertive vaginal intercourse (0.03-0.09%) - insertive anal intercourse (0.06%) - receptive oral sex (0-0.04%)

Answer 267

- access to appropriate treatment and care - reduction in morbidity and mortality - reduction of vertical transmission - reduction of sexual transmission - public health - cost effective

Answer 268

savings on social care, lost working days, benefits claimed, costs associated with further onward transmission

Answer 269

- be alert to circumstances appropriate to offer and recommend an HIV test - patients may have an unacknowledged but identifiable risk, or have signs and symptoms of HIV infection - HIV testing in GP would expedite referral directly to HIV services - misconceptions create barriers to uptake: pre-test HIV counselling is not a requirement; negative HIV test doesn't need to be disclosed on applications for insurance

Answer 270

- they don't think of HIV - underestimate the risk of HIV in their patients - failure to recognise HIV as a modifiable prognostic indicator - misconception that they need pre-test counselling - misunderstanding of the implications for insurance, etc - fear of offending the patient these concerns have been overcome in the antenatal setting

Answer 271

- sexual contact with people from high prevalence groups - MSM, IVDUs, sub-Saharan Afrca/Thailand/Eastern Europe/USA - multiple sexual partners - rape in high prevalence localities - vertical - patients may not admit risk factors or be unaware of their risks

Answer 272

- generalised lymphadenopathy - acute generalised rash - glandular fever/flu-like illness - think about seroconversion - prolonged episodes of herpes simplex - persistent frequently recurrent candidiasis - oral candida - indicators of immune dysfunction - recently developed or worsening skin conditions - odd looking mouth lesions - unexplained weight loss or night sweats - persistent diarrhoea - gradually increasing SOB and dry cough - recurrent bacterial infections including pneumococcal pneumonia

Answer 273

- multi-dermatomal shingles - unexplained lymphadenopathy - unexplained weight loss or diarrhoea, night sweats, PUO - oral/oesophageal candidiasis or hairy leukoplakia - flu-like illness, rash, meningitis - unexplained blood dyscrasias

Answer 274

- any competent healthcare professional - normalise the test: document verbal consent; determine how results will be given - written consent unnecessary - pre-test HIV counselling is not required

Answer 275

- venous blood sample is preferred - 4th generation HIV tests include p24 antigen and will detect the vast majority of infections at 4 weeks (if negative, repeat at 8 weeks if high index of suspicion) - high sensitivity and specificity - salivary antibody screening tests available

Answer 276

- finger prick blood - lower sensitivity and specificity - false positive and negative results

Answer 277

- outreach into community settings/non-specialist clinics - increase patient choice - increased access to testing and case detection - earlier diagnosis in non-healthcare seeking individuals - reduce risk of complications - reduce transmission

Answer 278

- anxiety - incubation/window periods - misdiagnoses - inadequate partner notification: reinfection; onward transmission

Answer 279

negative test - repeat if within window period positive result or result not clear - phone sexual health or ID for advice and arrange an appointment for within 48 hours - explain test is reactive and needs further investigation

Answer 280

- discuss soon after diagnosis - length of look back depends on individual circumstances - document discussion of safer sex practices and PEPSE - discuss reckless transmission

Answer 281

- enveloped viruses - viral genetic material is RNA which is copied into DNA by reverse transcription and incorporated into the host cell to allow gene transcription

Answer 282

orthoretrovirinae -> lentiviruses

Answer 283

genus of slow viruses with long incubation period

Answer 284

- bovine immunodeficiency virus - equine lentivirus - feline immunodeficiency virus - ovine lentivirus visna/maedi virus - primate lentivirus group

Answer 285

HIV-1 HIV-2 SIV (simian immunodeficiency virus)

Answer 286

deltaretrovirus | - HTLV 1 + 2

Answer 287

- HIV1 arose from transmission of SIV cpz from chimpanzees to humans pre-1950 - HIV2 arose from SIV sm

Answer 288

simian immunodeficiency virsues (SIVs) circulating in chimpanzees and/or gorillas from west Central Africa - SIVcpzPtt (Pan troglodytes troglodytes) - SIVgor (gorilla x3) - SIVcpzPts (Pan troglodytes schweinfurthii)

Answer 289

M (main), N (new), O (outlying), P

Answer 290

A-D F-H J-K - clade B predominates in Europe and USA - clade A in West and Central Africa - clade C in Southern Africa - some subtypes don't circulate on their own but as part of a mosaic virus due to genetic recombination

Answer 291

1. attachment: viral and cell receptors e.g. HIV (gp120 and CD4) 2. cell entry: only central viral core carrying the nucleic acid and some associated proteins enter the host cell 3. interaction with host cell: use cell materials (enzymes, amino acids, nucleotides) for their replication; subvert host cell defence mechanisms 4. replication: may localise in nucleus, cytoplasm or both; production of progeny viral nucleic acid and proteins 5. assembly: occurs in nucleus, cytoplasm or at cell membrane 6. release: by lysis of cell or by leaking (exocytosis) from cell over period of time

Answer 292

1. attachment 2. entry 3. uncoating 4. reverse transcription (error prone so genomic variability) 5. genome integration 6. transcription of viral RNA 7. splicing of mRNA and translation into proteins 8. assembly of new virions 9. budding

Answer 293

chemokine receptors - CCR5 for M-tropic (R5 strains) - CXCR4 for T-tropic strains which can predominate in some individuals - mutations in CCR5 gene can influence risk of infection

Answer 294

- 9kB - RNA genome - encodes 9 genes: Gag, Pol, Env, Tat, Rev, Nef, Vif, Vpr and Vpu

Answer 295

Gag, Pol, Env, Tat, Rev

Answer 296

- encodes structural proteins | - made as a polyprotein and cleaved by HIV protease

Answer 297

encodes the enzymes reverse transcriptase, integrase and protease

Answer 298

encodes the envelope proteins

Answer 299

increases infectivity

Answer 300

- contributes to viral replication | - enhances production of host transcription factors e.g. NF-kB

Answer 301

binds to viral RNA and allows export from nucleus, and regulates RNA splicing

Answer 302

CD4 T cells - memory CD45RO+ cells infected preferentially early on - naive CD45RA cells infected later on in infection by X4 virus macrophages (have CD4 and CCR5) possibly dendritic cells early on - can trap virus via DC-SIGN and transport virus to lymph nodes to infect T-cells brain microvascular endothelial cells, CD34+ bone marrow progenitors, astrocytes, renal epithelial cells

Answer 303

- humoral immunity - cell-mediated immunity lack of identification of protective immune responses remains a major barrier to development of an effective vaccine against HIV-1

Answer 304

neutralising antibodies - poor/slow to develop effectively - envelope glycoprotein (gp120) is poorly immunogenic and has high genetic diversity

Answer 305

CD8 - CTLs against HIV form and cause early decline in virus - CTL responses are quantitatively and qualitatively poor - virus escapes from CTL responses through mutations CD4 - paucity of virus specific CD4+ T lymphocyte responses - failure of CD4+ T-lymphocyte proliferation

Answer 306

- heterogenous group of individuals that don't progress to AIDS - no symptoms of infection or signs of AIDS after at least 7 years infection with CD4 count >600 cells/ml in the absence of treatment - genetic factors (e.g. CCR5 C32), host immune responses (e.g. vigorous CTL responses), differences in MHC I HLAs

Answer 307

- progressive decline in number and function of CD4 T-lymphocytes - excessive and inappropriate activation of immune system - decreased proliferation in response to antigens - skewing of CD4+ T cell receptor e.g. preferential involvement of memory T-cells - CD8+ T-cells show enhanced activation and decreased cytolytic and non-cytolytic function - B cells show enhanced activation and decreased proliferation resulting in increased non-specific but decreased specific Ab production - decreased NK, neutrophil and macrophage function - perturbed cytokine networks: decreased Th1 responses e.g. IL-2; increased Th2/Th0

Answer 308

- direct cytotoxicity of directly infected cells (but only 1:1000-1000000 cells in periphery directly infected) - activation induced death - decreased production (infection of CD34+ progenitors in bone marrow and infection of thymocyte progenitors and disruption of thymic microenvironment) - redistribution (significant trafficking of CD4+ T cells from periphery to lymphoid tissue) - bystander cell killing (gp120 binding to CD4 sensitising cells to apoptosis. Fas ligand upregulation by Tat)

Answer 309

- infection of CD34+ progenitors in bone marrow | - infection of thymocyte progenitors and disruption of thymic microenvironment

Answer 310

significant trafficking of CD4+ T cells from periphery to lymphoid tissue

Answer 311

gp120 binding to CD4 sensitising cells to apoptosis | Fas ligand upregulation by tat

Answer 312

sanctuary sites - genital tract - CNS - GI tract - bone marrow particular cells - macrophages, microglia - resting T-cells e.g. CD4+ CD45RO+ memory cells only support replication when activated

Answer 313

- MSM - heterosexual women - injecting drug users - commercial sex workers - heterosexual men - truck drivers - migrant workers

Answer 314

- nascent: <5% prevalence in all known subpopulations presumed to practice high-risk behaviour - concentrated: >5% prevalence in one or more subpopulations presumed to practice high-risk behaviour - generalised: >5% prevalence in general population

Answer 315

50% of all new infections occurring world-wide are in 15-24 year olds

Answer 316

behavioural change - education - condom use - needle exchange knowing your status - VCT (voluntary counselling and testing)

Answer 317

1. reduce sexual transmission of HIV by 50% by 2015 2. reduce transmission of HIV among people who inject drugs by 50% 3. eliminate new HIV infections among children and substantially reduce AIDS-related maternal deaths 4. reach 15 million people living with HIV with lifesaving ART 5. reduce TB deaths by 50%

Answer 318

- by removing foreskin, it reduces the ability of HIV to penetrate due to keratinisation of the inner aspect of the remaining foreskin - inner part of the foreskin contains many Langerhans cells that are prime targets for HIV; some of these are removed with foreskin - ulcers, characteristic of some STIs that can facilitate HIV transmission, often occur on the foreskin. likelihood of acquiring these infections is reduced - foreskin may suffer abrasions or inflammation during sex which could facilitate passage of HIV

Answer 319

- contains 1% tenofovir (drug used in ART) - controlled by women - decreased risk of HIV by 39%

Answer 320

- needle and syringe programmes - drug dependence treatment - in particular, opioid substitution therapy - close compulsory drug detention and rehab centres - management of TB and viral hepatitis

Answer 321

- 35% with no intervention | - <1% with HAART and no breast feeding

Answer 322

option A - antepartum zidovudine (AZT) from 14/40 - single-dose nevirapine (sd-NVP) at onset of labour - AZT and 3TC until 1/52 post partum - daily oral nevirapine for infant until all breastfeeding ends option B - 3 drug HAART from 14/40 until all exposure to breast milk has ended - daily oral nevirapine to the infant until 6/52 of age option B+ - life long ART for mother, regardless of CD4 count or clinical stage

Answer 323

- awareness - procurement/delivery - clinical services: staff, clinics, testing and monitoring facilities - cost/choice of drugs - adherence - efficacy - comorbidities

Answer 324

to identify people with HIV through the provision of quality services for individuals, couples and families - link individuals and their families to appropriate HIV treatment, care and support, as well as HIV prevention services, based on their status - support scale-up of high impact interventions to reduce HIV transmission and HIV-related morbidity and mortality (ART, VMMC, PMTCT, PrEP, PEP)

Microbiology 2 Flashcards

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