Download Clinical Manifestations of HIV2

Clinical Manifestations of HIV
Ardis Ann Moe, M.D.
Center for AIDS Research and
Education
Summary
• Know Who to Test
• Know Early Warning Signs of HIV
• Absence of Risk Factors Does Not Mean
Absence of Whoops Factors
• D.W., Diagnosed with AIDS 1993. CD4
count 110.
– Develops PCP, MAC, wasting disease,
peripheral neuropathy
– Tried on multiple HIV regimens: AZT,
D4t+3TC, and various protease inhibitor
combinations beginning 1996
• Now has MDR-HIV, CD4 count 8 in 2001.
• Begun on T-20, abacavir, 3TC, tenofovir,
lopinavir/ritonavir and soft gel saquinavir
• ($50,000/year treatment)
• CD4 count now 256, viral load
undetectable. MAC resolves.
• Working part time, raises 2 children. Wife
still HIV• Diabetes, cholesterol 356, triglycerides 780,
Cr 1.9, facial wasting.
Epidemiology
• 900,000 persons with HIV in US, 1/3
unaware
• Over half of new infections are among
African-Americans, and 30% of new
infections are in women
• MSM 42%, IDU 25%, heterosexuals 33%
• Young MSM African-American men in
New York; rate of seroconversion 15%/year
• Young MSM crystal meth users in Los
Angeles; rate of seroconversion 20%/year
• Overall increase in number of new HIV and
AIDS cases
• Seroconversion parties: bug-chasers and gift
givers
• Complacent attitude fostered by glowing
advertisements of perfect health while on
HIV medications
• Drug use drives much of this epidemic,
directly or indirectly
• Death rate about 15,000/year
• 40,000 new HIV cases/year
• Liver failure and bacterial pneumonia now
leading causes of death; OI related deaths
now less than 1/3 of cases
Routes of Transmission
• Blood products (100%)
• Pregnant mom to unborn child (40% if
breast feeding)
• Receptive anal intercourse(1%)
• Shared IDU(1%)
• Needlesticks(1/300)
• Insertive anal intercourse(1/1,000)
• Male to female = female to male (IF male is
uncircumscised) (1/1000)
• Oral-genital sex (1/10,000)
• Shared razors
• Shared toothbrushes
• Exposure to open skin lesions
How to Prevent Transmission
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Counsel at-risk groups
Offer HIV testing to all pregnant women
PEP for needlesticks (within 1 hour)
Treat infected persons with HIV meds
Reduce drug use in community
Treat STD’s
When to Offer HIV Testing
• Shingles in person <60
• Recurrent, unexplained vaginal yeast
infections (3+/year)
• All pregnant women
• Gay/bisexual men
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Unusually severe ear or sinus infections
Failure to thrive in children
Persistent diarrhea
Unexplained weight loss
Unexplained lymphadenopathy
• Person of African race with unexplained
kidney failure
• FUO
• Bacterial pneumonia in healthy young
person
• TB
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Primary pulmonary hypertension
Idiopathic Thrombocytopenic Purpura
Severe Seborrhea
Unexplained persistent leukopenia
• Any history of any STD, including warts,
hepatitis A, B, C, or GI parasites
• History of unexplained enteric infections,
especially Shigella
• Thrush
• B cell lymphomas
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Jail
Homeless
Cocaine use
Crystal meth or other substance abuse
And anyone who asks for an HIV test!
Types of HIV Tests
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Elisa with Western blot or IFA
Anonymous vs Confidential Testing
Rapid HIV tests becoming more available
Home HIV tests
Urine and saliva HIV tests
• M.V. 65 yo male presents for routine heart
valve surgery. Married, retired MD.
– Housestaff get HIV test without patient’s
consent. Patient is HIV+, CD4 count 420
Clinical Signs of HIV
• Onychomycosis
– Often seen in diabetics as well
– Indefinite treatment with itraconazole, lamisil,
etc.
Scabies
• Can be widespread over entire body, with
heavy encrustations of organisms:
“Norwegian” scabes
Looks like severe psoriasis
• Patients should be isolated
• Shingles
– Rare in young persons, but can occur in up to
10% of HIV+ persons
– More likely to occur when HIV meds started
– Shingles of the face may cause blindness from
corneal involvement
– Shingles may cause secondary skin infections
from staph, Group A strep
• Warts
– HPV can be widespread
– Cause of cervical cancer, and now responsible
for increasing number of cases of anal cancer in
HIV+ men
– Tends to recur; difficult to eradicate
• Peripheral neuropathy
– Can occur in up to 1/3 of HIV+ persons
– Many causes: HIV, CMV, diabetes, INH, HIV
meds, alcohol, etc
• Thrush, vaginal yeast infections
– Thrush usually occurs in the mouth a few
months to a few weeks before PCP or other
AIDS OI occurs
– Women have more severe and difficult yeast
infections
• Primary pulmonary hypertension
– Most cases occur in women
– Reversible with HIV medications
– Unknown mechanism
• ITP
– Auto platelet antibodies from HIV stimulation
of the immune system
– Best treated with HIV medications and gamma
globulin; possible splenectomy
Opportunistic Infections
• T.W. 25 yo woman presents with DOE and
fevers in 1997. CD4 count 45. Boyfriend
died of PCP in 1995.
• PCP has 50% mortality if diagnosed late;
5% mortality if diagnosed within 3 days of
admission
• Can present as normal CXR, normal LDH,
normal ABG’s
• Most commonly presents as unusually
severe DOE, cough and fever in previously
healthy person. CD4 count <200
• Can cause pneumothorax
• May be unilateral, apical, or with a pleural
effusion
• Usually dry sputum production, but
bacterial pneumonia often co-pathogen
• T.W. now with CD4 count 850 on HIV
meds, completed MBA, married,
undetectable
• She did not face up to her AIDS until she
got the same pneumonia that killed her
boyfriend
• TB
– Tenfold risk of progressive TB infection if PPD
positive (5 mm induration)
– More likely to have atypical presentation:
• Spine TB, TB pericarditis, lower lobe infiltrates
• DOT therapy standard of care
• J.F. 31 yo male presents with paraplegia
1996 CD4 count 11.
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TB of lower spine and skull
Treated with 4 TB drugs and HIV medications
Finally learns to walk again after 5 months.
Working full time now
Bacterial pneumonias
• K.L., 37 yo married woman presents with
lobar pneumona. Previously healthy.
• CD4 count 340, HIV+
• Husband HIV-, no other sexual partners, no
drug use, no transfusions, no needlestick
injuries (UCLA care partner)
• Treated in Kenya for malaria with
cholorquine injections
• Doctor gave her AIDS from a dirty needle
• She is classified as an IDU risk factor
• 1 of 7 deaths in AIDS still due to bacterial
pneumonias: unchanged since 1987.
• No effect of HIV meds seen
• Flu vaccines, pneumovaccines helpful
• HIV infected persons more likely to have
PCN resistant strains
• Kaposi’s Sarcoma
– Caused by HHV8 and co infection with HIV (or
other immune suppression)
– Usually presents on legs, arms, tips of ears.
– Can involve lymphatics and cause massive leg
edema
– Deaths usually from lung involvement
• Treated with chemotherapy (IV and topical)
– Radiation therapy to face helpful
– HIV meds alone will treat 1/3 to ½ of cases
– Also a sexually transmitted disease
• R.S. presents with new KS of his legs in
1983
– Finally dies of bacterial pneumonia at age 61 in
2003
– Worked full time until day before death
• Mycobacterium Avium Complex
– Blood, lymph nodes, liver, spleen most often
infected
– Presents as fever, night sweats, anemia,
hepatosplenomegaly in persons <50 CD4 cells
• CMV
– Usually presents as a retinal infection with
“floaters” in persons <50 CD4 cells
– Can also involve brain, intestines, esophagus
• R.G.
– 41 yo male with CMV retinitis and CMV
encephalitis in 1996. Comatose
– Sent to nursing home to die and started on
triple-drug therapy as a trial
• 1 month later, becomes a major irritant to
the nursing staff, who discharge him home
• Toxoplasmosis
– Parasite found in soil, cat feces, undercooked
meat
– 15% of US population colonized
– Presents as seizures, focal neurologic signs and
fever in persons <100 CD4 cells
• Occasionally presents as pneumonia or
retinal disease
• Treated with sulfadiazine and
pyramethamine
• S.M. 32 yo male, CD4 #10 1996
– Developed toxoplasmosis and has residual
basal ganglia injury
– Parkinson’s disease and permanent stutter
• Multiple ring enhancing lesions on CT with
contrast
• Can occur with other CNS diseases:
cryptococcus, CMV, lymphoma
• HIV encephalitis
– Progressive loss of brain cells and
encephalopathy due to cytokine poisoning
– Partially reversible with HIV medications
– Limited number of HIV meds penetrate bloodbrain barrier
• Cryptococcal meningitis
– Presents as fever, AMS, neurologic deficits,
seizures in persons CD4 <70
– A.H., 41 yo male, HIV+ x 8 years. Refuses
meds
– Brought in by wife in coma. +cryptococcal
meningitis
• Requires repeated lumbar taps to decrease
brain pressure
• Treated with 2 weeks of ampho B and 5 FC
• Recovers and back working full time
• Progressive Multifocal
Leukoencephalopathy
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Caused by JC virus, CD4 <50
Rapid loss of function—stroke-like events
Residual personality changes, blindness
Survival 50% at 1 year even with HIV meds
• If HIV untreated, survival 4 months
• G.I., 55 yo woman. In Hospital 9 months
for unexplained weight loss and leucopenia
• Finally gets HIV test and diagnosed with
PML.
• Fed through G-tube x 3 months
• After HIV meds and treatment with
cidofovir and steroids, learns to feed herself
and walk after 6 months.
• Takes dancing lessons and moves to Rome
because the shopping is better
• Still mad at me for taking away her driving
license
• Lymphoma
– Hodgkins and non-Hodgkins lymphomas
– Usually B-cell
– CNS lymphoma almost always associated with
AIDS
– Rapid progression to death unless AIDS and
lymphoma can be aggressively treated
• L.M., 33 yo male with AIDS and MDRHIV
– Presents with vertigo July 22, 2003. MRI
normal
– Presents with diplopia August 1. New mass on
MRI
– Dead from lymphoma August 19.
• Cryptosporidium
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Intestinal parasite, traveler’s diarrhea
Cholera-like secretory diarrhea
Up to 17 liters of diarrhea/day
Only known treatment: HIV medications to
improve immune system
– CD4 count <150
• L.O. 47 yo male
– Presents with cryptosporidium diarrhea in 1994
– Treated with TPN. Multiple line infections
– Dead in 6 months
• Wasting disease
– Progressive loss of muscle mass
– Usually associated with chronic diarrhea
– Multifactorial causes: food issues, dysphagia,
OI’s, HIV virus, low serum testosterone in men.
HIV Treatment Related Problems
• Lipodystrophy
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Fat accumulation
Lipoatrophy
Diabetes
Elevated cholesterol and triglycerides
• 75% of all patients on protease inhibitors
will have some problem with fat
accumulation or fat wasting after 2+years of
protease inhibitor therapy.
– Some contribution from stavudine
• Fat accumulation syndromes may be due to
interference between HIV protease
inhibitors and natural proteases that digest
fat molecules
• Fat atrophy syndromes may be due to
mitochondrial toxicity
• 55% of persons on protease inhibitors will
develop insulin resistance within 4 weeks of
treatment
• 16% develop elevated fasting glucose
• 7% develop frank diabetes
• Partially reversible by stopping proteases
• Family history, gender, race, obesity all
factors as well
• HIV virus itself
– HIV+ persons have elevated triglycerides, low
HDL cholesterol and more facial wasting than
HIV- persons, regardless of treatment
• White males over 40 more likely to develop
facial wasting
• Obese African American women most likely
to develop fat accumulation and diabetes
(neck collar fat, breast enlargement)
• Avascular necrosis
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Usually presents as sudden hip pain in men
Risk factors: use of prednisone, weight lifting
?megace, androgens
Seen before protease inhibitors
• Only treatment is with hip replacement or
other hip surgery
• Lactic acidosis
– Caused by all nucleoside-based HIV
medications
– Most commonly seen with D4T, DDI, and DDC
– Can cause death within 48 hours
– Indistinguishable from sepsis
• Treated with removal of HIV medications
and IV thiamine, riboflavin and L-carnitine
• Low level lactic acidosis may be causing
osteopenia in long-term HIV survivors
• Overall, survival of persons with AIDS
dramatically improved
• 6 month survival in 1985 to 17+ years
• #1 cause of death in young adults in US in
1995 to #14 cause of death 18 months later
• Key factor is to test persons who are at risk
for any reason, and refer for evaluation
• Treatment now delayed until CD4 count
<350, or symptomatic from HIV, or
pregnant
• Studies on treatment interruptions ongoing.