HIV Flashcards
cells infected by HIV
CD4 T cells
macrophages
dendritic cells
HIV important glycoproteins and their function
gp120 - binds CD4 receptor and co-receptor (CXCR4 or CCR5)
gp41 - promotes fusion of viral and cellular membranes
Risk of MTCT - without intervention
- with BF
- with HAART
15-40% without intervention
15-29% from BF
<2% with HAART
Acute HIV infection - time after
3-10 weeks
AIDS definition
CD4<14%
AIDs defining illnesses (opportunistic infections)
Clinical manifestiations of CD4 >200
usually asympt Skin candida vaginitis / oral Oral hairy leukoplakia Seb derm Shingles KS Ca CIN/Cx Ca B cell lymphoma Haem ITP anaemia Resp Bact pneumonia Recurrent URTIs Pulm TB Other Neuropathy
Clinical manifestations of CD4 100-200
can be asympt Resp PCP Histoplasmosis / coccidiomycosis Military/extrapulm TB Cardiomyopathy Neuro neuropathies / myelopathy Dementia PML Other wasting NHL
Clinical manifestations of CD4 <100
can be asympt Fungal candida oesophagitis Cryptococcus Viral disseminated CMV Bact disseminated MAC Parasite toxo Microsporidiosis Chronic cryptosporidiosis Ca CNS lymphoma
Benefits of ART
prevent OI, Ca Alter/reverse course of existing OIs Improve/preserve immune ftn ↓ Sx ↑ QOL Restore hope ↓ transmission
NRTI - least to most toxic (roughly)
Lamivudine 3TC Emtricitabine FTC Tenofovir TDF Abacavir ABC Zidovudine AZT Didanosine ddI Stavudine d4T
NRTIs active against hep B
lamivudine 3TC
tenofovir TDF
problem with abacavir (ABC) and how to prevent
hypersensitivity rxn 3-7% - mortality
predict with HLA-B5701 test
NRTI class toxicities
mitochondrial toxicity - neuropathy, LA lipodystrophy myopathy hepatitis pancreatitis hyperlipidaemia
Lactic acidosis RFs
female older age high BMI - esp d4T, ddI, combination + - esp 1st 3/12 Rx
Lactic acidosis Sx
A, N, V, AP pancreatitis, hepatitis SOB, arrhyth multi-organ failure, death = increased anion gap + lactate
Lactic acidosis management
- obtain venous sample w/o tourniquet
- stop ARV if symptomatic + high lactate
- supportive Rx
- no d4T, ddI or AZT in next regimen
- routine monitoring not required
NNRTI class toxicities
rash
hepatotoxicity
NNRTI features
long half-life 2-3 wks
lots of drug interxns
not active vs HIV-2 or group O
risk resistance
preferred TB PI
efavirenz
Nevirapine risk and RFs for it
hypersensitivity rxn (rash, hepatotoxicity) - esp men with CD4>400, women CD4>250
benefits of boosting PIs with ritonavir
increased PI level b/c of less metabolism from cyt p450 inhibition fewer pills more predictable efficacy and activity lower toxicity less resistance
preferred PI in pregnancy
lopinavir/ritonavir
IRIS DDx
relapse resistance drug toxicity new disease process - Rx dilemma: stop/continue ART, stop/change OI Rx, anti-infly agent, immunosuppressives
risks of starting ARV at low CD4
higher risk OI
higher risk toxicity
non-AIDS related complications more common (CVD, Ca, liver, renal disease)
ARVs to avoid in TB
PIs - interxn with rifampicin
NVP - use EFV instead (can use if needed)
Treatment failure WHO definition
Clinical - new/recurrent stage 4 condition (IRIS excluded)
Immunological - fall of CD4 to baseline / 50% from peak
Virological - VL >5000
Indications for TMP/SMX prophylaxis of toxo/PCP
CD4 not available - WHO stages 2,3,4 CD4 available - CD4<350 (LMIC) - WHO stages 3,4 Alt - all PLHIV
3 I’s for HIV/TB
Intensified case finding for active TB
Infection control for TB at all clinical encounters
INH preventive treatment - latent TB prevalence >30%
- all with documented latent TB
Meningitis in HIV pts - causes
cryptococcus TB syphilis bacterial - strep, listeria viral fungal lymphoma
CNS mass lesion in HIV pts - causes
Common - toxo * - tuberculoma - lymphoma Less common - cryptococcoma - PML - bacterial abscess - other (syphilis, tumor, Chagas, Nocardia, Aspergillus)
Rx crypto meningitis
ampho B + flucytosine / fluconazole 800mg
or flucyt+flucon 1200mg or flucon 1200mg
Rx cerebral toxo
pyrimithemine + sulfadiazine (+ folinic acid)
alt clind+pyrimeth, high dose TMP/SMX, dapsone, atovaquone
Radiologic characteristics of CNS masses in HIV
Enhancement with contrast - toxo (ring enhancing) - lymphoma (ring or diffuse enhancement) - tuberculoma (diffuse enhancement) Non enhancing - crypto -PML # lesions - toxo (multiple) - lymphoma (single / multiple) - tuberculoma (single / multiple)
5 min neuro screen:
strength ok but slow mentation
HIV dementia
5 min neuro screen:
cauda equina syndrome
CMV radiculitis
5 min neuro screen:
pain in feet, decreased DTRs
sensory neuropathy (‘d’ drugs)
seizures, focal deficits
toxo
subacute progressive deficits
PML
ICP elevation
crypto
most common cause of retinitis in AIDS
CMV
CMV retinitis lesions
2/3 unilateral
‘cheese and ketchup’
uveitis rare
CMV retinitis Rx
iv gangiclovir /
PO valganciclovir if lesions not sight-threatening
2-3 wks
follow with secondary prophylaxis
Common lung disease aetiologies in HIV
TB
PCP (pneumocystis jiroveci)
bacterial
fungal
Commonest cause of bacterial pneumonia in HIV
pneumococcus (100x increased risk)
CXR in HIV
normal - PCP, TB, fungal, bronchitis
Diffuse infiltrates - PCP, TB, fungal, KS, CMV, LIP
Focal airspace - TB, fungal, bacterial, nocardia
PTx - PCP
Nodules/cavities - TB, fungus, staph, nocardia, rhodococcus, KS, endocarditis
Adenopathy - TB, fungus, MAC, lymphoma
Pleural effusion - TB, bacterial, KS, lymphoma, uremia, CHF, hypoalbuminaemia
Normal CXR in HIV lung disease
PCP
TB
fungal
bronchitis
Diffuse infiltrates on CXR
PCP TB fungal KS CMV LIP
Focal lesions on CXR
TB
fungal
bacterial
nocardia
PTx on CXR
PCP
Nodules / cavities on CXR
TB Fungus staph nocardia rhodococcus KS endocarditis
Adenopathy on CXR
TB
fungal
MAC
lymphoma
Pleural effusion on CXR
TB bacterial KS lymphoma uraemia CHF hypoalbuminemia
Oesophageal disease in HIV
- aetiology
- sx
- management
candida CMV HSV TB fungi cancer idiopathic - CD4 <100 - dysphagia / odynophagia, CP - empiric Rx candida (fluconazole 100-200mg 2/wks); EGD & Bx if no response
Diarrhoea etiology in HIV
TB MAC bacteria (salmonella, shigella, E coli, SI bact overgrowth) protozoa (crypto, isospora belli, microsporidium, giardia, cyclospora, E histolytica, strongyloides) fungi (histoplasmosis) virus (CMV, HSV) HIV (AIDS enteropathy) malignancies (KS, lymphoma) drugs (PIs, ABx)
Etiologies if large volume diarrhoea
small bowel disease
- cryptosporidium
- microsporidium
- cystoisospora
- giardia
Etiologies if small volume diarrhoea
colitis / proctocolitis - tenesmus, bld, mucus
- shigella
- campylobacter
- C diff
- HSV
- CMV
Hepatobiliary disorders in HIV
Viral hepatitis OIs - MAC, TB, bartonella, endemic fungi Malignancies Drugs - HAART, anti-TB, ABx, statins, psy Cholangitis - MAC, crypto, microsp, CMV
Potential reasons for non infectious complications of HIV
chronic immune system stimulation chronic inflammation premature aging mitochondrial damage (esp d drugs, NRTIs) drug toxicity
Spectrum of HAND (HIV-associated neurocognitive disorder)
ANI - asympt neurocog impairment
MND - minor neurocog disorder
HAD - HIV-associated dementia
AIDS-defining cancers
Kaposi’s sarcoma
Primary CNS lymphoma
NHL
invasive Cx Ca
AIDS-associated cancers (not AIDS-defining)
primary effusion lymphoma
SCC conjunctiva
Cancers with increased incidence in HIV (not dependent on CD4)
liver cancer Hodgkin's disease anal cancer melanoma oropharyngeal cancer lung cancer
Cause of Kaposi’s sarcoma
Human herpesvirus 8
Anaemia in HIV - frequency
- causes
70-80% patients with advanced disease Anaemia of chronic disease Drugs - AZT, cotrim, dapsone, primaquine Infections - parvo B19, fungi, TB Nutritional - iron, folate, B12, scurvy, Cu Malignancies, myelodysplasia
Leukopenia in HIV - frequency
- causes
50% patients with advanced disease Due to HIV Drugs - AZT, cotrim, sulfas, pyrimethamine, ganciclovir, ABx Infections - MAC, TB, fungi, parvo B19 Malignancies, myelodysplasia
Thrombocytopenia in HIV - frequency
- causes
40% patients - may be early sign of HIV
Periph destruction due to autoantibodies
- HIV, drugs
BM probs - infections, malignancy
Bicytopenia / pancytopenia in HIV
- causes
Malignancies - lymphoma, KS Infections - TB, MAC, VL, parvo B19, histo, cocci, crypto Aplastic anaemia, myelodysplasia Nutritional Drugs
Dyslipidaemia in HIV - causes
HIV
ARVs - esp boosted PIs, also NRTIs, efavirenz
Why is CVD more common in HIV?
HIV - dyslipidemia - endothelial damage - vascular dysftn - chronic inflammation - procoagulant factors - lipodystrophy ART - dyslipidemia - endothelial dysftn - HT - insulin R - fibrinogen levels - lipodystrophy
Bone disease in HIV
High prevalence osteopenia (25-60%), osteoporosis (10%) Possible causes - HIV - cytokines - ARV - lifestyle - MN, hypogonadism, acidosis - vit D insufficiency - liver disease Increased # rate in HIv
Type of HIV most common in Western world
subgroup B, group M, type 1
Type of HIV most common sth Africa (worldwide)
subtype C, group M, type 1
Common toxicities with ARVs
AZT - anaemia
Tenofovir - tubular toxicity (take for hep B)
Lamivudine - lovely (& FTC) (like for hep B)
Abacavir - allergy affecting life
Efavirenz - effects on baby, eccentric dreams, excellent in TB
Nevirapine - nukes the liver, hypersens, near-normal CD4 esp a prob
Important ARV components in hep B pts
TDF + lamivudine/emcitrabine
Cotrimoxazole prophylaxis - indications and benefits
WHO clinical stage 2,3,4
CD4<200 for PCP/toxo
Benefits - reduced mortality by 50% in severely immune-suppressed HIV-infected adults initiating ART, for at least 72 weeks. - reduced malaria incidence in these pts
Most frequent life-threatening OI and leading cause of death in HIV
TB
Three Is strategy
Isoniazid preventive treatment (IPT)
intensified case finding (ICF) for active TB
TB infection control (IC)
(pre-ART care setting)