HIV Diagnostics and Non-Infectious Complications Flashcards
What type of virus is HIV?
Lentivirus genus belonging to the family Retroviridae.
What is the difference between HIV-1 and HIV-2?
HIV-1 is responsible for the majority of infections globally. HIV-2 has a lower virulence and infectivity and is largely confined to West Africa.
What cells does HIV target? [3]
- CD4
- Dendritic cells
- Macrophages
How does HIV fuse to cells?
gp120 with co-receptor CCR5 or CXCR4 bind to CD4
What increases the likelihood of HIV transmission? [3]
High viral load [most important]
Presence of other sexually transmitted infections (STIs) (especially those causing genital ulcerations).
High risk behaviors
Risk of HIV spread [NOTE]
Mother-to-child transmission (without breastfeeding) 30. Breastfeeding for 18 months 15. Needle-sharing injection-drug use 0.67 Receptive anal intercourse 0.5 Percutaneous needlestick 0.3 Insertive anal intercourse 0.065 Insertive penile–vaginal intercourse 0.05 Receptive oral intercourse 0.01 Insertive oral intercourse 0.005
Symptoms of acute/early HIV infection?
fever, malaise, myalgia, night sweats, weight loss.
Lymphadenopathy, particularly axillary, cervical, and occipital
Persistent generalized lymphadenopathy
sore throat, painful mucocutaneous ulcers
Generalized Skin Rash
Nausea, diarrhea, anorexia, weight loss.
What is Persistent generalized lymphadenopathy?
Lymphadenopathy in at least two areas for at least 3 months.
Common neurologic presentation of acute HIV?
HA is the most common symptom
Aseptic meningitis, acute inflammatory demyelinating polyneuropathy, or mononeuritis multiplex
What is a long term non-progressor in HIV?
HIV-infected individuals whose CD4+ count remains >500 cells/μL with a viral load <5000 copies/mL for at least 8 years despite not commencing ART.
What is an elite controller in HIV?
Maintain an undetectable viral load (i.e., plasma HIV-RNA remains <50 copies/mL) without commencing ART.
What diagnosis prompts universal HIV testing? [7]
HCV TB HBV Lymphoma Pregnancy IVDU STI
What are Fiebig stages?
This is the classification of serologic events associated with acute HIV infection.
List the Fiebig stages
I RNA + [day 3-8]
II p24 Ag + [day 7-14]
III Elisa IgM + [day 10-17]
IV Western Blot +/- [Day 15-23]
V Western Blot + to p24 core and env [antibody production], no antibody to p31/32 integrase [day 47-130]
VI Same as 5 but p31/32 integrase is now positive
What is the first line HIV test assay?
ELISA testing for both HIV-1/HIV-2 antibodies as well as the p24 antigen (a capsid protein of the virus).
If the HIV screen is positive, what is the next test in testing
Differentiation between HIV 1 and 2 with antibodies specific to each of the viruses.
What is both HIV 1 and 2 antibody differentiation testing is negative?
PCR [NAT] should be done for HIV 1 and 2
If negative it is likely a false positive screen.
Recommendation for breast feeding in an HIV infected mother?
AVOID
What is HIV-associated neurocognitive disorders (HAND syndrome)?
changes in memory, concentration, attention, and motor skills that cannot be attributed to an alternative cause
What are the three levels of impairment in HAND?
(1) asymptomatic neurocognitive impairment
(2) mild neurocognitive disorder
(3) HIV-associated dementia (HAD)
How dos HAD present?
Symptoms that wax and wane over time, including cognitive deficits, behavioral and mood changes as well as motor symptoms
How does the mild neuroconitive disorder in HIV present?
Primarily memory problems and generalized slowing in processing information. Overall, cognitive deficits may be described as mental slowing with impairment in higher executive functions leading to decreased ability to perform instrumental activities of daily living (IADLs)
Motor signs in HAND? [4]
Slowness in movement, hyperreflexia, frontal release signs, and dysdiadochokinesia.
Diagnosis of HAND?
Exclusion
HAND work up? [7]
Progressive multifocal leukoencephalopathy, malignancy, nutritional deficiencies (vitamin B12 deficiency), endocrine disorders (thyroid or adrenal dysfunction), substance abuse, psychiatric disorders or other dementia syndromes.
HAD MRI findings?
Symmetric, periventricular hyperintense lesions on T2-weighted sequences
What is CNS viral escape syndrome
HIV replication in the CNS leading to neurocognitive symptoms in patents who are virally suppressed on ART. Most patients have viral drug resistance in the CSF.
Work up and mgmt for CNS viral escape syndrome?
CSF HIV RNA must be evaluated for resistance with regimen based on results.
–> Typically efavirenz is avoided.
What is Distal symmetric peripheral neuropathies (DSPN)?
Symmetric, bilateral pattern of diminished sensation and reflexes typically starting in the toes spreading proximally in the lower extremities.
Drugs associated with DSPN? [8]
didanosine and stavudine, dapsone, isoniazid, ethambutol, nevirapine, thalidomide, and vincristine
Risk factors for DSPN? [4]
Poorly controlled HIV, age >50 years, metabolic syndrome, and substance abuse
DSPN presentation?
numbness and tingling in the lower extremities, decreased sensation in a stocking distribution and reduced deep tendon reflexes in the lower extremities
DSPN diagnosis?
Clinical
What is Vascular myelopathy
Vacuolization of the lateral and posterior columns of the thoracic spine leading to a spastic paraparesis, loss of sensation, and urinary incontinence.
Describe the relationship between ART and stroke?
Long term ART use may also lead to increased risk of stroke due to endothelial toxicity and vascular dysfunction.
Describe the rash of acute HIV exanthem and enanthem
non-pruritic rash involving the upper trunk, proximal limbs, and potentially the palms and soles. It can be seen in up to half of patients with acute infection. It typically resolves in 1–2 weeks
What is eosinophilic folliculitis?
Typically described in patients with advanced disease and is a pruritic skin eruption of follicular papules or pustules, predominantly located on the scalp, face, neck, and upper chest
Pathogenesis of eosinophilic folliculitis?
Infection (with bacteria, Pityrosporum yeast, or Demodex mites) or an autoimmune reaction to sebocytes.
Presentation of eosinophilic folliculitis?
Recurrent, pruritic, erythematous follicular papules and rare pustules (3–5 mm diameter) on locations of the body with more sebaceous glands.
Diagnosis of eosinophilic folliculitis?
Labs: High IgE and eosinophil levels
Dx: Punch biopsy
Treatment of HIV associated eosinophilic folliculitis? [3]
ART (resulting in resolution for most) and symptomatic management with topical corticosteroids and oral antihistamines.
Important endocrine side effect of ritonavir?
Cushing syndrome in patients also given any steroid; even a steroid as mild as nasal or inhaled fluticasone.
How might HIV lead to graves?
Consequence of IRIS 1-2 years following ART initation
What comorbid conditions with HIV are a/w low testosterone levels? [3]
advanced disease, protease inhibitors (PIs), co-infection with hepatitis C
Work up of suspected testosterone def in HIV patient?
- AM testosterone
- Free testosterone
- LH and FSH levels
How will primary and secondary hypogonadism look on labs
Primary: LH and FSH are high
Secondary: LH and FSH are low or inappropriately normal
Work up of primary hypogonadism in HIV patient [3]
prolactin level, iron studies, and evaluation of other hormones that reflect anterior pituitary dysfunction.
Work up of secondary hypogonadism in HIV patient
OI
Scrotal US
Mgmgt of hypogonadism
- ART
if no improvement testosterone
How does HIV lead to bone-mineral dysfunction
- HIV infection which is independently associated with lower bone mineral densities due to proinflammatory cytokines increasing osteoclastic activity.
- ART [specifically TDF]
What HIV medication is a/w vit D def?
efavirenz
In PLWH who should get DEXA scans?
all HIV-infected postmenopausal women and men >50 years of age.
Work up if you find OA or osteopenia? [5]
testosterone levels, PTH, TSH, 25-OH-vitamin D, and 24-hour urine calcium.
Risk factors for HIV osteonecrosis? [5]
White race, male, CD4 count <200 cells/μL, prior osteonecrosis, prior fracture, and having an AIDS-defining illness, prior PI use, EtOH, steroid use
Osteonecrosis diagnosis?
MRI
How does osteonecrosis present?
Joint pain. Classically in the hip but all joints may be effected.
What is AIDS wasting syndrome?
Weight loss over 3 months of more than 10% body weight with a disproportionate loss of lean body mass and sparing of body fat. Predictor of poor outcomes.
What lab is present with AIDS wasting syndrome?
Elevated triglycerides
Treatment of AIDs wasting syndrome?
ART.
What is lipoatrophy?
Loss of subcutaneous fat in the face (buccal and/or temporal fat pads), arms, legs, abdomen, and/or buttocks. However, lean tissue mass is typically spared
HIV medications that cause lipoatrophy? [5]
Older medications; stavudine and zidovidine
efavirenz, rilpivirine, and PIs may increase risk
Treatment of lipoatrophy?
- Change ART
2. In DM addition of thiazolidinediones
What is fat accumulation in HIV?
Excess of visceral adipose fat with normal subcutaneous fat resulting in increased abdominal girth. May also occur around the dorsocervical area (i.e., “Buffalo hump”), trunk, and upper chest. This can also be seen in visceral organs like the liver.
Diagnosis of fat accumulation?
physical exam findings (abdominal circumference in men >102 cm and women >88 cm).
Tx of fat accumulation?
Treatment consists of diet, exercise, and treatment of type 2 diabetes mellitus. Metformin
What condition in HIV might metformin make worse?
Lipoatrophy
Infections in HIV that lead to hypoplastic anemia? [2]
Parvo
MAC
HIV medication that causes macrocytic anemia?
zidovudine
HIV associated medications that can lead to neutropenia? [4]
zidovudine, TMP–SMX, ganciclovir, and hydroxyurea
Infections in HIV that lead to neutropenia? [2]
EBV, B19
How might HIV reduce platelet counts? [2]
- HIV infects megakaryocytes
2. IgG cross reactivity between platelet glycoprotein complex (GP)IIb/IIIa and HIV envelope glycoproteins GP 120/120.
Diagnosis of HIV associated thrombocytopenia?
Exclusion
Treatment of HIV associated thrombocytopenia? [8]
- ART
- steroids
- Intravenous immune globulin, and anti-D immune globulin.
Refractory cases: dapsone, interferon alfa, vincristine, and splenectomy.
Who gets HIV associated TTP
Advanced HIV, often co-infected with Hep C
Etiology of HIV associated TTP
HIV infection of endothelial cells leading to vWF release and depletion of ADAMTS13
Diagnosis of HIV associated TTP?
Exclusion
Shigella and E.coli ruled out
Treatment of HIV associated TTP?
ART
Plasma exchange
What is HIVAN?
HIV-associated nephropathy
Collapsing form of segmental glomerulosclerosis and can be seen after seroconversion and throughout disease progression, but is more common in patients with advanced disease. More common in African Americans
Presentation of HIVAN?
nephrotic range proteinuria
rapid decline in kidney function
Diagnosis of HIVAN?
Kidney biopsy
Treatment of HIVAN
- ART
- ACE/ARB
- Nephro referral
What is fanconi syndrome
Loss of the following in the urine..
- Protein
- Glucose
- Potassium
- Phos
- Aminoacids
- Bicarbonate
NOTE: NOT ALL MAY BE PRESENT AT ONCE [may be only a few]
What HIV medications increase risk for cardiovascular events?
lopinavir–ritonavir and indinavir
Etiology of pericarditis in HIV?
- Bacteria
- Fungal
- Cancer
What is HIV-associated pulmonary hypertension?
Result in part from vascular changes resulting in remodeling of the media and adventitia of the arterial pulmonary tree, the extracellular matrix and plexiform lesions induced by infection with HIV-1.
Treatment of HIV-associated pulmonary hypertension?
epoprostenol, inhaled prostacyclin, inhaled iloprost, bosentan, and sildenafil in addition to initiation of ART.
What is Nonspecific interstitial pneumonitis in HIV?
Seen in PLWH with CD4 <200
Prevalence and etiology is not known
Diagnosis of nonspecific interstitial pneumonitis in HIV?
Exclusion of other infections
Clinical manifestations of Lymphocytic interstitial pneumonitis in HIV patients?
diffuse lymphadenopathy
peripheral CD8+ T lymphocytosis
Imaging findings vary in chest radiographs from normal to diffuse alveolar, nodular, or interstitial infiltration.
Diagnosis of Lymphocytic interstitial pneumonitis?
Exclusion of a pathogen on biopsy. Typically lymphocytic infiltration is seen and plasma cells. Septal infiltration differentiates LIP from NIP.
Treatment of LIP?
ART
Treatment of COP?
ART, steroids
What is HIV enteropathy?
HIV infection of enterocytes, leading to loss of gastrointestinal mucosa and increased permeability. Also, faster intestinal transit times may result from HIV directly damaging the autonomic nerves of the intestine
Diagnosis of HIV enteropathy?
Exclusion, exclude infections
NOTE:
ART may cause diarrhea that is self limiting over 8-12 weeks
Cause of salivary gland enlargement in HIV patient?
Cysts or lymphocytic process that is different than sjogrens
Treatment of salivary gland disease and xerostomia in HIV?
Salivary gland stimulation
What is Diffuse interstitial lymphocytosis syndrome (DILS)?
characterized by CD8+ T-cell infiltration of multiple organs can manifest with bilateral parotid gland. lung infiltration as a lymphocytic interstitial pneumonia may occur, other organ systems that may be affected include nervous system, liver, kidneys, and digestive tract.
Treatment of DILS?
ART
Steroids as 2nd line
Cause of acalculous cholecystitis in HIV pt?
Associated with infection with CMV or Cryptosporidium.
What is AIDS cholangiopathy?
Dilated intra- and extrahepatic biliary ducts and presents with right upper quadrant pain, icteric sclera, and elevated alkaline phosphatase.
Cause of AIDS cholangiopathy?
Advanced AIDs
CMV or cryptosporidium less commonly
Presentation of Kaposi sarcoma?
Cutaneous disease appears as red or violet macules, papules, or nodules in various sizes up to several centimeters in diameter. Extracutaneous involvement can be respiratory, mucosal, or GI. Oral involvement most commonly involves the palate or gingiva and is present in about a third of PLWH with KS.
Diagnosis of KS?
Biopsy, CXR and stool for occult blood to r/out lung and GI involvement.
Treatment of KS?
ART
liposomal doxorubicin or liposomal daunorubicin if progressive or visceral disease
What is Multicentric Castleman’s disease?
Lymphoproliferative disorder characterized by angiofollicular lymph node hyperplasia associated with HIV and human herpesvirus 8 (HHV-8) infection as well as other malignancies including concomitant KS.
Presentation of Multicentric Castleman’s disease?
Fever, fatigue, generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia. Usually non-white men age 50-65 with CD4 >200
Diagnosis of Castleman’s?
Biopsy
Treatment of Castleman
Steroids
Rituximab if refectory
What infections with HIV puts you at risk for Non-Hodgkin lymphoma?
HHV-8, EBV
Risk factors for PLWH to develop Non-Hodgkin lymphoma [5]
CD4 counts <100 cells/μL high HIV viral loads family history Not being on ART. co-infected with hepatitis B or C
Treatment of Non-Hodgkin lymphoma?
cyclophosphamide, doxorubicin, vincristine (Oncovin), and prednisone (CHOP) or CHOP–rituximab (CHOP-R) with concurrent initiation of ART.
What is Primary effusion lymphoma?
Rare type of NHL that occurs exclusively in PLWH
A/w HHV-8
Grows in body cavities (pleural, pericardial, and peritoneal) as lymphomatous effusions that are not associated with a mass.
Diagnosis of primary effusion lymphoma?
cytology of the pleural fluid.
What are the AIDS related lyphomas? [4]
Diffuse large B cell lymphoma
Burkitt’s lymphoma
Plasmablastic lymphoma
Hodgkin lymphoma
Describe the pathology of Diffuse large B cell lymphoma
large, atypical lymphoid patterns that express pan-B cell antigens.
Describe the pathology of Burkitt’s lymphoma
starry-sky” pattern with prominent cytoplasmic vacuoles in monomorphic, medium-sized cells with multiple nuclei.
Presentation of Plasmablastic lymphoma
presents in the oral cavity and is driven by HHV-8 infection. They are very aggressive and have a poor prognosis.
Describe the pathology of Hodgkin lymphoma
Reed–Sternberg cells seen
Presentation of Primary central nervous system lymphoma
confusion, memory loss, focal neurologic deficits, and seizures as well as B symptoms
What will imaging show with a primary CNS lymphoma?
solitary or multiple mass lesions may be seen, Lesions also may be ring enhancing or have enhancement that is irregular or patchy.
How does primary CNS lymphoma differ from toxo on imaging? [3]
- Toxo will have multiple lesions, CNS lymphoma is typically single.
- CNS lymphoma is large [typically >4cm]
- CNS lymphoma is typically NOT in the posterior fossa
Diagnosis of primary CNS lymphoma?
LP if no mass effect [only helpful in 15% of cases]
Brain biopsy is gold standard
Treatment of primary CNS lymphoma?
Methotrexate
Presentation of anal cancer?
itching, rectal bleeding or discharge, and tenesmus; however, most patients are asymptomatic.
Anal cancer screening in PLWH? [3]
Anal cytology among the following risk groups:
MSM
women with history of anal intercourse or abnormal cervical Pap smears,
those with genital warts.
Treatment for anal cancer if small?
<1cm base: topical therapy with trichloroacetic acid and imiquimod
Treatment for anal cancer if larger?
infrared coagulation and anoscopy-directed lesion ablation
What is ragged red fiber disease?
This is ZDV induced myopathy [nucleoside induced myopathy]. Rare now, used to be due to pts being iatrogenically overdosed with ZDV
Treatment of methhemoglobinemia?
Stop offending drug [often dapsone]
Methylene blue if methemoglobin level is >30%
In whom does methylene blue not work?
Those with G6PD def
How might early treatment of acute retroviral syndrome complicate HIV testing?
Early treatment may blunt humoral immune response and confirmatory assay may become unreliable.
How is HIV-2 different from HIV 1?
HIV-2 is..
- Less pathogenic
- Less likely to transmit to baby
- Less likely to have kaposi sarcoma
- Instrinsically resistant to NNRTI and fusion drugs
Where is HTLV-1 prevelant?
Japan and South East Asia [30-50%]
Indigenous tribes in Australia [up to 40%]
Caribbean
How is HTLV-1 transmitted? [4]
Sex
Breastfeeding
IVDU
Drug transfusion
How is HTLV-1 diagnosed?
Blood serology
ELISA with confirmatory western blot
What disease does HTLV-2 cause?
NONE!
It is a distractor.
How might HTLV-1 present
95% asymptomatic In a patient from the right endemic area.. Recurrent pneumonia with bronchiectasis TB, MAC, leprosy PCP Recurrent strongyloides Scabies, Norwegian scabies Hypercalcemia + lytic bone lesions Uveitis Lymphocytic pneumonitis
What malignancy may complication HTLV-1?
Acute T-cell leukemia
Treatment of Acute T-cell leukemia in HTLV-1?
AZT+lfn
Lenalidamide
Mogamulizumab
What virus causes tropical spastic paraparesis?
HTLV-1
Presentation of tropical spastic paraparesis?
Spastic paraparesis with lower > upper
Proximal > distal muscles
There is hyperreflexia, urinary incontinence
+ Babinski reflex
Who gets tropical spastic paraparesis?
Jamacians [Caribbeans]
F > M
Treatment of HTLV-1 TSP/HAM?
Corticosteroids may slow progression
–> ART is NOT effective.
What is a “flower cell”
Lymphocytes with HTLV provirus present
Occurs in higher frequency with acute t-cell leukemia and HAM/TSP. Seen on peripheral blood smear.
NOT associated with disease
NOTE:
Home HIV testing may have false negative results in the first 3 months of infection.
How often should those on PrEP be followed
Every 3 months with HIV testing
