HIV & STI's Flashcards

Question

Cryptococcomas: How treated? What is response to treatment? What is usual organism?

Answer 1

* treatment same as cryptococcal mengitis * i.e. (iv ampho (preferably Abmisome) + oral flucytosine) x 2 wks followed by oral fluconazole x 8-10 weeks * flucytosine hard to get because one company makes it an upped the price * early in therapy new lesions may arise and existing lesions may enlarge as result of inflammatory response to treatment * does not mean failure and lesions tend to shrink over time as treatment continued * Cryptococcomas usuall C. gatti, not in immunocompromised pts

Answer 2

* invariably fatal without treatment * with treatment mortality remains at 25% * 40% have neurological deficits including * Loss of vision * cognitive impairment * cranial nerve palsies * hydrocephalus may be late complication * relapse in up to 25% * some pts may need life-long antifungals

Answer 3

* reactivation of latent *Toxoplasm gondii* * indolent over several days * hypodense, ring-enhancing lesions, esp basal ganglia and thalamus

Answer 4

1. Binding: virus binds to CD4 recepter and co-receptor on target cell 2. Fusion: the viral envelop merges with cell membrane and spills its contents into cell 3. Reverse transcription: the viral RT enzyme is used to make a DNA copy of the viral RNA 4. Viral DNA is integrated into the host cell genomic DNA located in the cell nucleus - using the enzyme ***integrase*****.****** * once integrated viral DNA is known as proviral DNA and cannot be removed without destroying host cell * proviral DNA is transcribed by host cell into mRNA and used to make viral proteins that will form the components of a new virus 5. Budding: components of new virus leave the host cell by budding, using the host cell wall as the envelope of new HIV virion 6. ***Protease*** cleaves the long chain polyprotein into active components eg. viral enzymes. Virus now capable of infecting other cells

Answer 5

* 2013 guidelines say start ART when CD4 \<500 cells/m³ or for WHO stage 3 or 4 disease although each country will have own guidelines * 2015 say start when dx of HIV +ve is made regardless of CD4 * goal is to maintain viral suppression for life

Answer 6

* Available: * Reverse Transcriptase inhibitors * Nukes * non-nukes * Protease inhibitors * Not * CCR5 receptor antagonists * Fusion inhibitors * Integrase Strand Transfer Inhibitors

Answer 7

1. Tenovovir (TDF) 1st NRTI-nucleoside reverse transcriptase inhibitor 2. Lamivudine (3TC) 2nd NRTI 3. Efavirenz (EFV) NNRTI - non-nucleoside rti

Answer 8

1. renal impairment (prox tubular nephropathy with proteinuria, hypophosphatemia) 2. osteoporosis * (Good against Hep B) * 245 mg daily * nrti

Answer 9

* 3TC * generally well tolerated * rarely peripheral neuropathy * good against Hep B * 300 mg daily or 150 mg bid * nrti

Answer 10

1. Rash 2. psychiatric symptoms (dizziness, vivid dreams, insomnia, psychosis) 3. hepatotoxicity * 600 mg daily * NNRTI

Answer 11

* 1st NRTI: * Tenovofir (TDF) 245 mg od or * AZT 250 mg bid or * Abacavir * 2nd NRTI: * lamivudine (3TC) or emtricitabine * NNRTI * Evavirenz (EFV) or nevirapine (NVP)

Answer 12

* AZT * 250 mg po bid * adverse effects: * anemia (macrocytic) * nausea * lipodystrophy

Answer 13

* ABC * 600 mg daily * 1st NRTI 1. hypersensitivity in those with HLA-B5701; rash & flu like illness; less common in African population 2. Nausea, anorexia 3. Controversial evidence of increasing CV risk

Answer 14

* FTC * NRTI, prescribed in most regimens as 2nd NRTI * 200 mg od * Generally well tolerated * Rarely pruritis, hyperpigmentation

Answer 15

* NVP * NNRTI, 3rd drug * 200 mg od for 2 wks then 200 mg bid * a/e similar to efavirenz * mild rash during first 6 wks - continue * SJS/TEN discontinue

Answer 16

* 1st NRTI * Tenofovir or zidovudine or abacavir * (TDF or AZT or ABC) * 2nd NRTI * Lamivudine or emtricitabine * (3TC or FTC) * NNRTI * Efavirenz or nevirapine * (EFV or NVP)

Answer 17

* in event of treatment failure 1. change the 1st nrti eg TDF to AZT or ABC 2. stay on 3TC or FTC 3. change from NNRTI to **protease inhibitor, i.e** 1. ****Lopinavir/ritonavir (LPV/r) or 2. Atazanivir/r (ATZ/r)

Answer 18

* used to boost concentration of other PI's by inhibiting cytochrome CYP3A4 in intestine and liver; no activity at doses used to boost * a/e 1. hyperlipidemia & triglyceridemia 2. hepatitis 3. pancreatitis

Answer 19

* LPV/r * 400 mg/100 mg bid * boosted PI, 3rd drug in 2nd line regimen 1. diarrhea common, tx loperamide 2. hepatic dysfx

Answer 20

* ATZ/r * 300 mg od/100 mg * boosted PI/ 3rd drug in 2nd line regimen * a/e * hyperbilirubinemia/assymptomatic icterus * diarrhea - tx loperamide

Answer 21

* 2 nrti + 1 nnrti: 1st line combinations * Trioday * tenofovir/lamivudine/efavirenz * (TDF/3TC/EFV) * 300 mg/300 mg/600 mg 1 tab daily * Viraday or atripla * tenofovir/emtricitabine/efavirenz * (TDF/FTC/EFV) * 300 mg/200 mg/600 mg 1 tab daily * Triomune 40 * stavudine/lamivudine/nevirapine * (D4T/3TC/NVP) * 40 mg/150 mg/200 mg, 1 tab bid * **no longer recommended by WHO because of neuropathy**

Answer 22

* Combivir * AZT/3TC 300 mg/150 mg bid * Truvada * Tenofovir/emtricitabine 245 mg/200 mg od * (TDF/FTC) * Kivexa * abacavir/lamivudine 600 mg/300 mg od * (ABC/3TC) * **In 2nd line treatments; must be combined with boosted PI**

Answer 23

* Pathogenesis: reactivation of latent *Cryptococcus neoformans* infection. * Presentation: most commonly meningitis, can include blurred vision due to raised ICP, seizure (due to parenchymal cryptococcoma) or confusion * Neuroimaging: meningitis, cryptococcomas, gelatinous pseudocysts * Complications: communicating hydrocephalus, IRIS with ARV

Answer 24

* around 90% or greater

Answer 25

* It is a function of how many mutations are required for resistance & how easily such mutations occur. * Lowest: * NRTI's: 3TC, Emtricitabine (FTC) * NNRTI's: Efavirenz (EFV) & NVP * Moderate: * Tenofovir (TDF), AZT, ABC, d4T * High: * PI's: Lopinavir (LPV), Atazanavir (ATZ), Darunavir (DRV)

Answer 26

* VL should be fully suppressed by 9 months after starting successfull ARV. * Check at 6 months. Should see significant downward trend at least below 1000 copies/ml. * WHO recommends q 12 month monitoring while on ART (but q 6 months preferred if resources allow.)

Answer 27

* Pathogenesis: reactivation of latent *Toxoplasma gondii* infection. * Presentation: non-specific, indolent over several days. * Neuroimaging: hypodense, ring-enhancing lesions, especially **basal ganglia, thalamus.**

Answer 28

HIV viral genotyping for resistance. The *pol* gene. 20%

Answer 29

* worldwide distribution * seroprevalence varies from 15% US & Canada to 50-88% in Europe and Africa

Answer 30

* CD4 generally \< 100, very rare above 200 * commonest cause of CNS mass lesion in an HIV person, even in TB endemic areas. * rare in children * in HIV persons with CD4 \<100 and where not on toxo prophlaxis there is a 30% chance of developing cns toxo

Answer 31

* usually present with focal signs realating to one or more brain mass lesions * defuse encephalitis can occur * headache, confusion, fever, behavioural changes and altered mental status common * focal neuro deficits an seizures common * expyramidal sx due to affinity for basal ganglia * onset may be insidious ro rapid

Answer 32

Primary CNS lymphoma tuberculous granulomata or abscess ?PML

Answer 33

* In **Acute Infection:** * IgG and IgM negative at onset. * IgM rises first, +ve within 1 wk * IgG +ve by 2 weeks * However, CNS toxo **almost always reactivation**, serology +ve in 85% of cases * Absence of Ab's makes dx less likely but **negative serology does not exclude CNS toxo as loss of AB may occur with immunosuppression** * IgM rarely +ve, usually not helpful * PCR testing variable sensitivities and specificities

Answer 34

* MRI more sensitive than CT * usually multiple solid or cystic spherical lesion with ring enhancement, surrounding edema and mass effect * may be anywhere but predilictino for grey/white interface or basal ganglia * the more lesions there are, the more likely the cause is toxo

Answer 35

* neither MRI nor CT can differentiate among many possible etiologies of brain lesions in AIDS pts * DDX * Cryptococcus * Histoplasmosis * Aspergillosis * **Tuberculosis: tuberculoma may look very much like toxo. Look for meningeal enhancement.** * Trypanosomiasis * cysticercosis * angiostrongylus cantonensis * CNS lymphoma * PML * single lesion favours lymphoma * CNS tuberculomas look similar to toxo: 60% will have abnormal CXR * Progressive Multifocal Leukoencephalopathy does not produce mass effect

Answer 36

* LP frequently contraindicated due to mass lesion, usually not needed as suggestive radiology with +ve serology sufficient to start presumptive treatment * CSF: * usually mononuclear pleocytosis with normal glucose ratio. * toxo pcr specific but low sensitivity * CSF Ab's not helpful * CNS lymphoma: EB virus may be present * TB: CSF PCR +ve in 60% of cases

Answer 37

1. IgG positive 2. No effective prophylaxis was being taken AND 3. There are multiple ring enhancing lesion on the neuroimaging * If all 3 not present then biopsy or other dx tests should be performed * eg PCR for EBV, Tb, Cryptococcus neoformans * If no response within 2 wks then consider brain biopsy * With **single** cerebral lesion, particularly if serology neg then consider biopsy to r/o CNS lymphoma

Answer 38

* 1st line: * (pyrimethamine + sulphadiazine **or** clindamycin) x 6 wks * (nb also covers against PJP) * Adverse effects: * Pyrimethamine mylotoxic, must be given with folinic acid. Rash, nausea, vomiting * sulphadiazine: rash, fever, leukopenia, hepatitis, n, v, crystalluria * clindamycin: rash, fever, n, v, c. diff. * Alternatives: * pyrimethamine + folinic acid + azithromycin * pyrimethamine + folinic acid + atovaquone * sulphadiazine + atovaquone * co-trimoxazole as for PJP

Answer 39

* careful clinical neuro f/u needed * if no clinical or radiological improvement within 2 wks of tx, then dx prob not toxo * consider alternative dx, brain biopsy * after 6 weeks reduce doses to prophylactic doses

Answer 40

* steroids may be necessary for raised icp but minimize duration to minimize risk of oi's * CNS lymphoma may improve with steroids so complicates trial of treatment * anti-convulsants for seizures only, NOT seizure prevention * 86% improve by day 7, 90+% by 2 weeks * surgical decompression rarely necessary

Answer 41

* Primary prophylaxis: * All IgG +ve patients with CD4\<100 should start prophylaxis with co-trimoxazole * if allergic consider desensitization * alternatives include dapsone + pyrimethamine or high dose dapsone * discontinue if CD4\>200 for 3 months * Secondary prophylaxis * following treated cns infection, continue maintenance until CD4\>200 for 6 months and restart if falls below 200 again * secondary prophylaxis same drugs as treatment but half the dose

Answer 42

* depends on immune restoration * residual neuro impairment in 40% * seizures common * relapses common, even remotely and at higher CD4 counts

Answer 43

* Pathogenesis: reactivation of latent CMV infection * Presentation: very advanced immunosuppression, cd4\<50 * non-specific cognitive decline, less often meningism and/or focal findings * retina "bushfire" appearance, "tomato ketchup" * Neuroimaging: meningoencephalitis

Answer 44

* Urgent: * suspected CNS infection * suspected subarachnoid hemorrhage * Non-urgent: * Idiopathic Intracranial hypertension * NPH * Carcinomatous meningitis * CNS vasculitis * Other CNS infections: e.g. syphilis, lyme disease * consider in MS, paraneoplastic syndromes, Guillain Barré syndrome

Answer 45

* usual adult volume 150 ml * secreted by choroid plexus * approx 500 ml/day = 0.35 ml/min * turnover 14% per hour (i.e. 100% in about 7 hrs)

Answer 46

* **R**espiration: irregular breathing/tachypneia * **O**culocephalic reflex: absent - Dolls eyes movement * **P**osture: decorticate or worsening decerebrate * **E**yes: poor or absent response to light/ fixed/dilated pupils * **Y**uk: bradycardia and hypertension

Answer 47

1. local superficial infection at LP site 2. shock 3. extensive or spreading purpura 4. coagulation abnormalities * prolonged inr * platelets \< 100 x 10⁹/L * receiving anticoagulant therapy 5. respiratory insufficiency

Answer 48

* may be difficult, based on * toxo more likely to be multiple * toxo more likely to be frontal/basal ganglia/parietal vs periventriculare, frontal, cerebellar, temporal for cns lymphoma * see diagram

Answer 49

* no or rare mass effect * 50% are solitary lesions * typical location: subcortical white matter, cerebellum, brainstem * 25% show enhancement * corpus callosum can be involved, sparing grey matter and cortical ribbon * caused by JC (John Cunningham) virus

Answer 50

* 5 times as common 1. direct damage from HIV virion 2. indirect damage from inflammatory cells 3. atherogenic effects of antiretrovirals

Answer 51

* Oral Hairy Leukoplakia * first described 1984, non-HIV 1999 * EBV-related in setting of immunosuppression * Tx: * Gentian violet/retinoids/podophylin/acyclovir cream * Tx superadded infections * ART! * **WHO STAGE III**

Answer 52

* Esophageal Candidiasis * 2 weeks fluconazole 50-200 mg/d * **WHO Stage IV**

Answer 53

* CMV esophagitis * cd4\<50 * linear/longitudinal ulcers * "Owl's eyes" inclusion bodies on biopsy * Concurrent retinitis? * IV gancyclovir 2-4 weeks * HSV esophagitis * oropharyngeal ulcers more common * well circumscribed "volcano-like ulcers" * eosinophilic inclusions * Aciclovir 14 days * Esophageal candidiasis * treat 2 wks fluconazole 50-200 mg daily * Non-Infectious * Peptic * Cancer (HPV 22%)

Answer 54

* 15 to 25% of infants infected during pregnancy, labour & delivery * 5-40% infected during breastfeeding, the longer breast-fed the more the risk * overall 15-45% of infants will be HIV infected * With ARV risk reduced to \<5%

Answer 55

* Pregnancy * **High viral load** * placental infections * STI's * maternal malnutrition * anemia * Labour and delivery * **High viral load** * rupture of membranes\>4 hours * Invasive delivery procedures * premature birth * Low birth weight infant * Breast Feeding * **High viral load** * Mixed feeding * duration of breastfeeding * breast abscesses, mastitis etc * oral disease in baby * maternal malnutrition

Answer 56

1. primary prevention of HIV infection among women of childbearing age. 2. preventing unintended pregnancies among women living with HIV 3. preventing HIV transmission from pregnant women living with HIV to their infants 4. providing appropriate treatment, care and support to mothers living with HIV and their children and their families.

Answer 57

* start pregnant HIV +ve mom on appropriate ART to continue for life. * Babe to start Nevirapine od or AZT bid until 4-6 weeks * start co-trimoxazole from 4-6 weeks to 18 months if proven HIV negative * encourage breast feeding, discourage mixed feeding for first 6 months

Answer 58

1. Nevirapine once daily x 6 weeks 2. (Nevirapine od + AZT bid) x 6 weeks 3. (Nevirapine od + AZT bid) x 12 weeks

Answer 59

* All HIV exposed children from 4-6 weeks of age should be on cotrimoxazole prophylaxis until 18 months of age (when off breast mild and HIV ruled out) * all HIV infected children should remain on lifelong cotrimoxazole prophylaxis

Answer 60

* daily oral tenofovir disoproxil fumarate (TDF) or coformulated TDF/emcitabine in areas of high HIV prevalence to prevent HIV acquisition in pregancy * potential to complement existing prevention strategies * high risk groups * serodiscordant couples * sex workers * ?adolescents

Answer 61

* Kaposi's sarcoma stomach * Throughout GIT * often aggressive, blood loss * Tx: chemo: vincristine, bleomycin * WHO Stage IV

Answer 62

* Chronic diarrhea implies WHO stage III

Answer 63

* salmonella sp * shigella spp * campylobacter spp * E. coli (ETEC/EAEC) * C. dificile * also * C. Perfringens * Yersinia enterocolitica

Answer 64

* greater risk of prolonged infection/invasive disease * 2-300 times increased risk of invasive nontyphoidal salmonella in advanced HIV * may be recurrent, in which case WHO Stage IV * 40 fold increased risk of *Campylobacter jejunii* in AIDS * worse outcomes, mortality up to 40%

Answer 65

* lymphogranuloma venereum * caused by chlamydia trachomatis infection, serovars L1-3 * endemic in Africa and Caribean * causes inguinal buboes * DX by PCR when available * associated with ulcerative rectocolitis in MSM * appearance indistinguishable from IBD * Treatment: tetracyclines & macrolides

Answer 66

* Prolonged / fever / abdominal pain / blood -\> treat: * •Ciprofloxacin/azithromycin 3-5 days * •Nb Cipro resistance, esp in South Asia * •Know local resistance * If no response: Treat for amoebic dysentery * Metronidazole 800 mg tds x 5-10 days * If no response: * Stool for ova and parasites * Look for other causes of diarrhoea

Answer 67

* initial seroconversian related diarrhea * then causes as HIV disease progresses * CD4 ~400: * Bacterial infection * Tuberclosis * *Isospora belli* * *CD4 ~ 200* * *Cyclospora cayatanensis* * *Strongyloides* * *CD$ ~ 100* * *Cryptosporidia* * *microsporidia* * *GI malignancies* * *MAC* * *CMV*

Answer 68

* Parasitic * *Cryptosporidia* spp. * *Cyclospora* spp. * *Isospora belli* (now cystioisospora) * *Microsporidia* (*Enterocytozoon bienneusi* and *Encephalocytozoon intestinalis)* * *Viral* * *CMV* * *Fungal* * *Histoplasmosis* * *Cryptococcosis* * *Mycobacterial* * *TB* * *MAI*

Answer 69

* *Cryptosporidium parvum* * ubiquitous coccidial protozoa * causes 5-10% of diarrhea in the immunocompetent * nb Milwaukee outbreak * can cause significant chronic diarrhea if CD4\<100 * Microscopy: modified acid fast stain oocyst 3-6 µm diameter, PCR, ELISA * Treatment * nitazoxanide * paramomycin * **START ART**

Answer 70

* Isospora belli * protozoal parasite * human only host * endemic in Tropis and subtropics * unusual cause of diarrhea without immune suppression in temperate areas * may cause chronic diarrhea in HIV, usually with CD4 2-300 * Diagnosis: Acid fast stain. PCR. * Treatment: Co-trimoxazole - response rates up to 100% * **ART**

Answer 71

* microsporidiosis * Trichrome stain for diagnosis * rare in humans with normal immune system * CD4 usually\<100 * most intestinal infections due to *Enterocytozoon bienusi/intestinalis* * *Treatment:* * *Albendazole* * ***START ART***

Answer 72

* Cytomegalovirus * herpes DNA virus * CD4\<50 * 15% of chronic diarrhea * Clinical: diarrhea, cramps, tenesmus, fever, abd pain, wt loss, melena * Complications: enteritis, colitis, ulcers, appendicitis, ileocecal obstruction, toxic megacolon, perforations, GI hemorrhage * Diagnosis: Biopsy, direct EM visualization, ELISA, PCR * Treatment: IV ganciclovir, valaganciclovir (foscarnet, cidofivir) * "CMV is a nightmare."

Answer 73

* chance of extrapulmonary or disseminated mycobacterial infection increase with reducing CD4 count (Usually \< 50) * colitis, terminal ileitis possible but relatively rare * MAI may present as diarrhea * MTB less likely to present as diarrhea

Answer 74

* in 50% no cause is identified * Neoplastic * Lymphoma * Kaposi's sarcoma * Drugs (HAART) esp PIs * HIV Enteropathy * Pancreatic disease * ddi (didanosine)

Answer 75

* Effects * villous blunting, inflammation and malabsorption * reduced micronutrient absorption * reduced fat absorption * ?increased motility * marked early reduction in gut CD4 in excess of total body CD4 loss * Management * **ART** * antimotility agents (crofelemer?) * probiotics? * Zinc? * thalidomide?

Answer 76

* all ARV's but PI especially * Diarrhea accounts for 20% of all missed doses * 2-4%: Darunavir, Atazanavir * 12-50%: Saquinavir, Ritonavir. Kaletra (lopinavir/r), Nelfinavir * Antibiotics * NSAIDS * Propranolol, methyldopa * Digoxin * Metformin * Laxatives * Traditional and complementary medicines

Answer 77

* good history: alcohol, drugs, endocrine * Examination * Investigations: * 30-40% parasite found * \>50% no infectious etiology * Rule out malaria * Stool: what is available? x 3 samples * Wet prep * Culture * Staining for OCP (Zn, trichrome) * Molecular * 50% no pathogen found * Flex sigmoid or colonoscopy: Yield 27-39% * If no dx, after available investigations proceed to treatment algorithm

Answer 78

* **1. Co-trimoxazole 960 mg qid x 7 days** * (Isospora, cyclospora, Cryptosporidium, bacterial infections) * If no response: * **2. Metronidazole 400 mg tid x 10 days** 1. (Giardia, Clostidium, E. Hystolytica, Microsporidia) * If not response * **3. Albendazole 400 mg bid x 21 days** * (Microsporidia, enteric helminths)

Answer 79

* increased probability of transmission * **Increasing viral load** * man infected * anal vs vaginal sex * man not circumcised * concurrent STI's * Younger age * Host genetics * violent sex * African countries * Viral Type * **Acute and advanced HIV stage** * Increased number of contacts * multiple concurrent partnerships? * because of increasing rate of infecting new partners at time of seroconversion * increased duration of infectiousness * ?suboptimal ART

Answer 80

* 26 fold increase in relative transmissability * during acute seroconversion and * at advanced stage of HIV (low CD4) * see attached graph

Answer 81

* Cohen 2011 RCT of ART immediate vs delayed to CD4 350-500 in HIV discordant couples * demonstrated 93% durable reduction in transmission to HIVE neg partner in immediate treatment group * START (2015) study shows major reduction in disability, disease and death in early ART groupl * WHAT SUPPORTING EVIDENCE DO WE HAVE FOR TASP? * Biological plausibility * Mathematical modelling evidence of high potential for effectiveness * Individual-level evidence of protective efficacy * Ecological evidence of prevention of transmission * Strong evidence for improved clinical outcomes * Prospective individual-level evidence of cost-effectiveness * Is this enough? * No randomised evidence yet on effect on HIV incidence at community level (But coming soon!) * Affordability * Operational and implementation science * Surveillance for outcomes under programmatic conditions

Answer 82

* Pre-exposure prophylaxis: the use of antiretrovirals in HIV uninfected individuals to block the acquisition of HIV viral infection. * may be daily or intermittent prior to risk exposure

Answer 83

* much less than commonly perceived per event * e.g. receptive anal intercourse 1.1%; insertive .06% * receptive vaginal intercourse 0.1%; insertive .08% * receptive oral sex .02%; insertive oral sex 0% * needlestick injury 0.3%

Answer 84

* Assess⇒Counsel & support⇒Prescribe⇒Follow-up * (TDF & 3TC/FTC ) + LPV/r (or ATV/r) * ideally within 2 hours, but up to 72 hours * Prescribe for 28 days, test at 3 months post exposure

Answer 85

* Broad differential diagnosis! * Viral: viral hepatitis (HBV / HCV), HIV * Mycobacterial: MTB complex and non-tuberculous mycobacteria * Fungal: cryptococcus, histoplasmosis, candidiasis, PCP * Parasitic: liver flukes, cryptosporidium, microsporidium * Malignancy: lymphoma and Kaposi sarcoma * Drugs: allARVs–ATV/NVP/3TC/EFV/DDI... Plus anything that effects HIV negative individuals! * Plus anything that affects HIV-negative individuals!

Answer 86

* TB therapy * rifampicin * izoniazid * pyrazinamide * ARV's * nevirapine * ddi, d4T (mitochondrial toxicity) * abacavir hypersensitivity (associated with HLA - B\*5701 -rare in African pop) * Atazanavir (unconjugated hyperbilirubinemia) * - ... * Drug interactions - esp PI's * [http://www.hiv-druginteractions.org](http://www.hiv-druginteractions.org) * [http://www.hep-druginteractions.org](http://www.hep-druginteractions.org)

Answer 87

* the possibility of IRIS-associated hepatitis is a particular concern * Approach: * Full clinical assessment - US if possible * Consider drug induced hepatitis if: * AST/bili\>5xULN, or 3.5 x baseline * coagulopathy, eosinophilia, rash, lactic acidosis * Consider TB IRIS if: * evidence of IRIS in another system * New tender hepatomegaly * predominantly cholestatic * ultrasound: diffusely abnormal liver texture, LN, normal biliary tree * Stop treatment: * ALT/AST * \>5 times ULN without symptoms * \>3 times ULN with sx (anorexia, nausea, abd pain) * sig rise in bili * Restart treatment once bili normalised or ALT/AST \< 2xnormal * If infectious/unwell then for 'holding regimen' * ethambutol and * moxifloxacin or streptomycin

Answer 88

* IRIS is a consequence of excessive **pathogen- specific** immune recovery reaction * occurs in a subset of patients on antiretroviral therapy (ART). * Infective forms * present as ‘unmasking’ of a previously subclinical infection or * paradoxical clinical deterioration of treated infection * most important risk factors for IRIS: * low CD4+ T-cell count * short time between treatment of infection and commencement of ART * Treatment * continue ART * provide antimicrobial therapy for the provoking infection * most cases self- limiting * mortality and hospitalisation esp high for CNS TB or cryptococcus * Corticosteroid therapy **should be considered** in certain forms of IRIS after the exclusion of other conditions * Prevention * start ART with CD4\>350 will prevent most

Answer 89

* mycobacteria * TB - start ART within 2 weeks after starting TB treatment to reduce mortality * consider steroids with CNS disease * non-tuberculous * including BCG IRIS * cryptococcal infections * consider steroids with CNS disease * Viral infections - in general don't use steroids with exception of CMV eye disease where IRIS likely response to residual antigen * Herpes, warts, molluscum contagiosum - don't use steroids * CMV - retinitis and uveitis likely due to residual antigens - usually responds well to topical or systemic steroids * JC Virus/PML - controversy about steroids, likely don't use * Hepatitis B & C * ?neuro IRIS caused by HIV * Kaposi's sarcoma: may get paradoxical worsening after starting ART, usually delayed by few months. Treatment with chemo may be necessary. Prevent by treating severe forms of KS prior to starting ARV. * Parasitic Infections * toxoplasmosis * schistosomiasis * strongyloides stercoralis * leishmaniasis * cryptosporidium

Answer 90

* TB treatment should be initiated first * followed by ART as soon as possible within the first 8 weeks of treatment (Strong recommendation, high certainty in the evidence). * HIV-positive patients with profound immunosuppression (e.g. CD4 counts less than 50 cells/mm3) should receive ART within the first 2 weeks of initiating TB treatment

Answer 91

* CDC * defines AIDS as CD4\<200 **plus** Aids defining Condition * WHO * staging clinical only to allow definition of treatment failure on clinical grounds if cd4 not available * Stage 1: assymptomatic or lymphadenopathy only * Stage 2: mild OIs or wt loss * Stage 3: More serious OIs, more severe wt loss * recurrent infections * pulmonary TB or (scrofula in kids) * cytopenias * Stage 4: AIDS defining conditions * OI's, cancer, organ failure

Answer 92

* 2 wks of amphoB + fluctyosine for induction followed by 10 weeks of fluconazole * According to this article, for induction: * 1 wk of amphoB + flucytosine or * 2 wks of fluconazole + flucytosine * followed by 10 wks of fluconazole

Answer 93

* Progressive multifocal leukoencephalopathy (PML) is a rare and usually fatal viral disease characterized by progressive damage (-pathy) or inflammation of the white matter (leuko-) of the brain (-encephalo-) at multiple locations (multifocal) * caused by JC virus * usually seen in advanced HIV, sometimes associated with biologic agents/monoclonal Ab's

Answer 94

* In untreated HIV infection, with breastfeeding, around 30% of infants will become infected. * The risk is not eliminated by avoidance of breastfeeding, but is reduced to around 20%, since there is also a risk during gestation and delivery. * The risk is not eliminated by Caesarian section, but in untreated HIV infection it is reduced. * The most significant factor in transmission risk is maternal viral load. Women can be advised that they can choose vaginal delivery if the viral load is undetectable on treatment at that time. * In developed settings, vertical transmission of HIV is very rare, thanks largely to antiretroviral treatment of pregnant women and avoidance of breastfeeding.

Answer 95

* sulfadiazine + pyrimimethamine x 6 wks or * or sulfadoxime pyrimethamine (Fansidar) 2 tabs bid x 6 wks or * cotrimoxazole * (these may be more readily available in resource-limited settings) * ART should be started if new dx HIV and should be followed by secondary prophylaxis with either cotrimoxazole or same drug fr treatmet at half dose

Answer 96

* One of four distinct cardinal signs guides the therapeutic approach: urethral discharge, vaginal discharge, genital ulceration and bubo. The WHO proposes a flowchart based on urethral discharge (men), vaginal discharge, lower abdominal pain (women) and genital ulceration (either sex). The syndromic approach has dramatically reduced STIs in East Africa. Remember that HIV becomes more virulent and far more easily transmitted in the presence of an STI in either partner.

Answer 97

* The five Cs are Counselling, Confidentiality, Contact tracing, Compliance and Condoms. The nine elements of the management of STIs are history, physical examination, diagnosis, early effective treatment, advice on sexual behaviour, promotion and provision of condoms, partner notification and treatment, and case reporting. Add a tenth, clinical follow-up. In all cases one must take account of the patient’s genuinely held ethical values, whether one disagrees with them or not, provided they are not clearly damaging to others. The provision and teaching of how to use well-designed flow charts is vital in the provision of any STI service.

Answer 98

* (a) Treponema pallidum (b) Herpes simplex virus (HSV-1, HSV-2) (c) Haemophilus ducreyi * (d) Lymphogranuloma venereum (Chlamydia trachomatis) - painless ulcers (e) Epstein-Barr virus (EBV) Chancroid is caused by H. ducreyi, a gram-negative bacillus. This condition is extremely common in developing countries. It is characterized by a ‘soft chancre’ in contrast to the ‘hard chancre’ of syphilis. The chancre quickly becomes a painful ulcer. ‘Kissing ulcers’ are common in females and spread by direct contact from one labium to another. As expected, dyspareunia and dysuria are frequent symptoms. Chancroid is an important risk factor for HIV and should be vigorously treated with azithromycin, quinolones, erythromycin or ceftriaxone. Tetracyclines are ineffective. * Herpes Simplex causes painful genital ulcers. * T. pallidum causes syphilis while EBV causes infective mononucleosis and herpes simplex-like lesions called Lipschütz ulcers or "ulcus vulvae acutum". * Symptomatic EBV shows clusters of inflamed papules and vesicles on the genitalia resembling cold sores. HPV (human papilloma virus) is the most common sexually transmitted infection. More than 40 types of HPV are infectious and these may affect the mouth and throat as well as the genitalia. HPV is important in that some types can initiate carcinoma. The current vaccines only offer protection against a few specific types of HPV. * Do not confuse HSV (herpes simplex virus) with HPV (human papilloma virus).

Answer 99

1. TBM: (within) 2 wks with CD4\<50 * otherwise upon completion of TB intensive phase (8wk) * start steroids with tx of TB meningitis 2. CM: 2-4 wk seems obtimal 3. Toxo: little data but early seems appropriate 4. PML: early cART

Answer 100

* Targets? * 90% hiv +ve diagnosed * 90% treated * 90% virally durally suppressed * Obstacles * delay dx, lack of care facilities * Home dx HIV * decentralization of care * home visits and home start of ARV * task shifting

Answer 101

* Bacteria * **Strep. pneumoniae**, staph, Klebsiella * NTS, pseudomonas, H flu, Mycoplasma * Rhodococcus equi, Nocardia (tend to mimic Tb) * Mycobacteria (Tb and non Tb) * consider Tb even in acute cough * Fungi * Pneumocystis jirovecii (PCP) * crypto, histo, penicillium, coccicoides, candida * aspergillus * Viruses * flu, adeno, rhino, cmv ...

Answer 102

* Against TB - INH * against pneumonia - cotrimoxazole, PCV * cotrimoxazole reduces mortality, pneumonia, malaria, hospitalization, diarrhea * **therefore where malaria and/or severe bacterial infections prevalent WHO recommends starting Cotrimoxazole prophylaxis regardless of CD4 or stage** * stop smoking * hiv test and ART

Answer 103

* **Tb - use steroids with TB tx** * malignancy eg lung, other solid organ tumors, hematological * Kaposi's * pyogenic bacterial infection * uremic * other transudative * connective tissue * trauma/post-op * idiopathic

Answer 104

* cats definitive host, excrete oocysts in feces, rodents are usual intermediate host * humans accidental host, ingest oocysts, disseminate to tissues and encyst as bradyzoites * tachyzoites develop from oocysts or bradyzoites, travel to liver, taken up by macrophages, disseminate esp to brain and muscle and then give rise to cysts * Aquisition: 1. ingesting oocysts from contaminated water, food, soil or cat feces 2. ingesten of tissue cysts (bradyzoites) in raw meat (important in France) 3. vertical transmission pregnancy 4. less commonly blood transfusion or 5. unpasteurized goats milk

Answer 105

* when acquired late in pregnancy * 15% in 1st trimester * 71% after 36 wks

Answer 106

* serology may be negative * +ve serology indicates past infection but negative does not exclude it * MRI findings do not differentiate amongs multiple possible etiologies including * crypto * histo * lymphoma * tb * trypanosomiasis * cns lymphoma * **However, toxo findings do not include meningeal enhancement, which would point more towards tb or crypto**

Answer 107

* mononuclear pleocytosis with normal glucose ratio * pcr specific but low sensitivity * csf ab testing unhelpful, don't do it * EBV by PSR indicates primary CNS lymphoma * PCR may be pos for TB (60% of abscesses)

Answer 108

6 wks * pyrimethamine + sulfadiazine + folinic acid * alternatives include * pyrmimethamin + folinic acid + azithrom * pyrimethamine + folin acid + atovaquone * sulfadiazine + atovoquone * cotrimoxazole in pcp doses * short term steroids may be indicated but complicate interpreting response to tx becuase cns lymphoma tx or tb sx may improve with this

Answer 109

* toxo * this is true even in regions where TB is endemic

Answer 110

* yes, in 20% of cases * chest xray may show diffuse pul infiltrated, lobar consolidation or cavitatin lesions that may resemple tb

Answer 111

1. 30% of world population has latent TB 2. HIV increases liftime risk of dev TB by \>20% 3. Risk is high from acute seroconversion to HIV on and then it rises as CD4 falls. 4. 15% of TB pts worldwide are coinfected with HIV 5. 79% in SSA. 11% in Asia

Answer 112

1. Establish **I**ntensified Case Finding. 2. Introduce **I**zoniazid Preventive Therapy * minimum 6 months ?up to 36 * if available and feasible TST prior and start IPT on those +ve 3. Ensure TB **I**nfection control measures in health care.

Answer 113

1. Although studies have shown benefit with those TST or IGRA positive, WHO suggests offering it where feasible, but testing is not necessary before starting INH. 2. IPT reduces risk of developing TB by about 30%(actually prob a bit more). 3. INH should not be offered to TST neg pts. 4. 6 months, but some evidence to suggest benefit prolonged with 36 months. 5. To all of them.

HIV & STI's Flashcards

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