Clinical Conference on HIV/AIDS
Dr. Ardis Moe
Page 1
HIV Clinical Conference
August 26, 2002
Ardis Ann Moe, M.D.
UCLA Center for AIDS Research and Education
Brief overview of HIV opportunistic infections:
M.V.
Presents with PCP, thrush, oral HSV,and onychomycosis
Later develops MAC and CMV retinitis.
Survives 2 1/2 years with AIDS in era of AZT monotherapy.
Pneumocystis carnii Pneumonia(PCP)
Still the most common presenting infection for persons with AIDS overall
(usually in persons with no previous medical care for HIV)
Fever, cough (dry or productive), and dyspnea are triad of symptoms
Usually cough is first symptom--"doc, I’ ve had a cold for a month"
Usually treated as bronchitis or sinusitis, which it clinically can
resemble (and can occur simultaneously in AIDS patients)
Clue is worsening after 2-3 weeks of routine antibiotic therapy for
sinusitis/bronchitis (Amoxicillin, erythromycin)
Mortality decreased from 50% in 1981 to less than 5% overall now--due
to earlier detection and better treatments.
PCP causes avelolitis--which leads to decreased oxygen diffusion
(decreased DLCO) and will ultimately lead to ARDS.
Cavity formation by organisms leads to spontaneous pneumothorax, a
hazardous complication of PCP.
Spontaneous pneumothorax in a febrile patient--PCP until proven
otherwise.
Treatment of severe PCP can actually precipitate ARDS--release of il1 and TNF.
Use of prednisone (40 mg po BID x 5 days, 40 mg po q Day x 5 days, then
taper over next 11 days) is key to preventing ARDS in patients with PaO2
70 or less, or A-a gradients 35 or greater.
Reduces mortality by 50%, and need for intubation by 50% when
prednisone is used with Bactrim or pentamidine.
Severe PCP--treated with Bactrim and steroids, or pentamidine with
steroids
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Dr. Ardis Moe
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Salvage therapy: trimetrexate or IV clindamycin + primaquine (G6PD
positive only) with steroids.
Mild PCP--oral bacrim, oral dapsone + trimethoprim, oral atovaquone,
oral clindamycin + primaquine. Steroids not needed. (PaO2 greater than
70, A-a gradient less than 35, good access to medical care--follow-up
twice weekly until symptoms improved)
Diagnosis
Induced sputum (50% sensitivity at UCLA)
BAL
BAL with biopsy
Open-lung biopsy
Prophylaxis
Bactrim 1 double-strength tablet daily (minimum 3x/week)
Dapsone 100 mg daily
Aerosolized pentamidine 300 mg every month
atovaquone 750 mg BID
Failure rate less than 5% on daily bactrim; 7-10% on dapsone
and atovaquone; up to 20% on aerosolized pentamidine.
Patients on aerosolized pentamidine tend to present with upper-lobe
infiltrates, or fever with pneumothorax, or Pneumocystis carnii in eye, GI
tract, bone marrow, or sinuses.
R.L. 40 yo married man with weight loss, anemia and fevers to 102 x 6
months.
P.K.
CD4 count 10. Given ritonavir, saquinavir, D4T and 3TC. Then develops new mass in
his abdomen and fevers.
Atypical presentations of MAC while on protease inhibitors--new FUO,
lung, abdominal masses or new lymphadenopathy. New huge granulomas
forming around masses of MAC.
Mycobacterium Avium Complex
Caused by Mycobacterium Avium (usually AIDS patients) or
Mycobacterium Intracellulare (usually non-AIDS patients on high-dose
prednisone)
Fever, night sweats weight loss, anemia in persons with CD4 cell counts
less than 50 are classic signs of MAC.
40% of FUO cases in persons with HIV are due to MAC.
Prophylaxis should be given to patients with CD4 counts less than 50;
azithromycin 2 tabs/week--biaxin 1 tab BID, or rifabutin 2 tabs/day.
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Dr. Ardis Moe
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Prophylaxis with weekly Azithromycin is cheaper and involves fewer pills
for the patient to take.
Diagnosis is by isolation on blood culture (Isolator tubes) or isolation from
normally sterile sites: bone marrow, lymph nodes, abscesses.
Treatment: (Clarithromycin or high dose Azithromycin) + ethambutol+
rifabutin.
R.G.
CMV encephalitis, retinitis wheelchair bound and on TPN. Sent to a nursing home to die
and given new meds: indinavir, AZT, and 3TC as a last resort.
Adherence issues--patients who only partially take protease inhibitor
combinations will have only short-term benefits, and then resistance
strains are selected for and can be transmitted to others.
Difficult drug regimens, side effects, number of pills, drug and alcohol
abuse and depression all limit the ability of the patient to take pills
regularly.
Cytomegalovirus(CMV)
CMV disease in the pre-protease inhibitor era affected 40% of persons
with AIDS
Now, new CMV retinitis is a rare entity.
85% as retinitis, a viral infection of the retina
Presents as a new increase in "floaters", blurring of vision,
or sudden retinal detachment in persons with CD4 counts
less than 50.
Blindness can occur in less than two weeks from the onset
of symptoms, so rapid diagnosis with a dilated eye exam by
an AIDS-savvy ophthalmologist is essential.
Treatment options have expanded dramatically over the past
2 years:
Oral ganciclovir
Ganciclovir implants
IV ganciclovir
IV foscarnet
Combo tx with ganciclovir and foscarnet
Intravitreal foscarnet or ganciclovir
Cidofovir,
vitrevene (antisense CMV codons)
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Dr. Ardis Moe
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Treatments require knowledge of the location of the CMV disease, the
other medications that the patient is taking, previous use of anti-CMV
medications, impact on quality of life of the medications, and assessment
of risks and benefits.
15% of CMV disease presents as extraocular disease, usually esophageal,
duodenal, biliary, colonic CMV.
GI CMV occurs at slightly higher CD4 counts-up to 100 whereas the
majority of CMV eye disease occurs in CD4 counts less than 50.
Fever, abdominal pain, and bloody diarrhea are the hallmarks of CMV
colitis
Many of these patients have simultaneous CMV eye disease.
CMV vitritis can occur as CD4 counts rise after HIV therapy started
J.C.
History of PCP, adherent to daily Bactrim. Widespread KS, not interested in
chemotherapy.
Presents with new pneumonia.
Kaposi’ s Sarcoma
Now thought to be caused by a sexually-transmitted type of herpes virus,
HHV-8 (also known as KSV) that leads to malignant transformation of
endothelial cells.
Usually begins on extremities (legs, arms, tip of nose)
Oral KS indicates a higher risk of pulmonary KS
Pulmonary KS can be fatal secondary to massive pleural effusions and
tumor overgrowth of lung.
A variety of treatments are effective: topical retinoic acid formulation;
limited radiation for KS of legs, face, mouth;liposomal doxirubicin, ABV,
taxol, VP-16, for more advanced disease.
D.B.
Decides to stop his 3x/week Bactrim because it was "too many pills".
Presents with fever, cough,stiff neck, and a swollen leg.
Cryptococcal meningitis
Median CD4 count 68 at diagnosis.
Presents with fever, seizures, headache, stiff neck, vision changes,
"stroke-like" appearance.
Diagnosed after CT or MRI of brain and spinal tap
Mortality has decreased from 50% to less than 10% with aggressive
treatment
IV amphotericin B + 5 FC
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Dr. Ardis Moe
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oral fluconazole + oral 5FC for mild cases
Oral fluconazole after initial therapy to prevent relapse—If
CD4 counts rise over 200 can stop fluconazole
R. B.
4 children, 2 dead from AIDS, now pregnant for the fifth time. In a coma from PML
(progressive multifocal leukoencephalopathy) and transferred in from her nursing home
for monitoring during her seventh month of pregnancy.
Progressive Multifocal Leukoencephalopathy
Caused by JC viral infection of the brain in an immunosuppressed person;
presents as progressive loss of motor and sensory functions--"strokelike". Some dramatic improvements seen if protease inhibitors are
initiated.
L.O.
Forgets to wash his hands while on board ship in the tropics. Presents with
cryptosporidium diarrhea and develops wasting syndrome. "slim disease".
Cryptosporidium
Severe diarrheal illness--up to 17 liters of diarrhea/day
Prevents absorption of food, medications. Patients are often TPNdependent
Best treatment--improve immune system with antiretrovirals
S.M.
Presents 50 kg weight, fevers, cryptosporidium and microsporidium diarrhea,
toxoplasmosis, HIV dementia and Protein S. deficiency with DVT’ s.
Toxoplasmosis
Exposure to toxoplasmosis occurs asymptomatically in 10-15% of US
persons.
Risk factors: exposure to soil (gardeners), cat feces, eating
undercooked meat, esp lamb.
Presents as fever, seizures, confusion, coma, "stroke-like" appearance.
Typical lesions in brain—multiple ring-enhancing
Can occur simultaneously with other brain diseases (CMV, cryptococcus,
lymphoma). Treated with sulfadiazine, daraprim, or clindamycin and
daraprim.
G.I. 55 yo married female with progressive depression, weight loss and
WBC 2.0
HIV Dementia
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Dr. Ardis Moe
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Progressive neurologic disorder, involving short-term memory loss and
psychomotor dysfunction.
Caused by progressive loss of brain neurons. Reversible to some degree
with antivirals, but only a limited number of the anti-HIV drugs penetrate
the brain (abacavir, nevaripine, D4T, 3TC, AZT)
C.S.
Purple skin lesions. Has cats at home.
Bartonellosis
Bacillary epitheliod angiomatosis--caused by Bartonella henselae;
organism related to those causing "cat scratch disease" and "trench
fever". Treated easily with various antibiotics: rifabutin, Cipro,
Azithromycin. Often mistaken for Kaposi’ s Sarcoma
M.J. 30 yo married man. Develops shingles.
J.G. 35 yo married man. Wife has severe primary pulmonary hypertension.
F.H. 44 yo pregnant woman, married, 5 healthy children, immigrant from United Arab
Emirates.
M.G.
Pregnant with her second child, first one is sick from AIDS. Husband unaware of his
wife’ s HIV, and still having unprotected sex with her.
Risks of domestic violence, abandoment, and need to keep pregnant
women on anti-HIV drugs during pregnancy can interfere with public
health interests.
Who to test for HIV: shingles in a person less than 60, unexplained fevers,
weight loss, or chronic diarrhea. Tuberculosis (50% of TB cases
worldwide TB-associated). Sudden onset of bacterial pneumonia in an
otherwise healthy young person with no obvious risks for pneumonia (like
alcoholism or smoking). Unexplained lymphadenopathy. Primary
pulmonary hypertension. Failure to thrive in children. Dementia in
persons less than 70. Homelessness. Jail. IDU. History of transfusions
outside of US, Canada, Western Europe, Japan, and Australia after 1985.
Immune thrombocytopenic purpura (ITP). 3+ episodes of severe
unexplained vaginal yeast infections in a year for an otherwise healthy
(nondiabetic) woman. Severe dysplastic Pap smears in a young woman.
History of any STD: hepatitis A, B, C, warts, herpes, GC, chlamydia,
syphilis, salmonella, shigella, campylobacter, cryptosporidium, giardia,
Entomeba histolytica, (15% of heterosexuals engage in rectal sex). gay or
bisexual men. ALL PREGNANT WOMEN NEED TO BE OFFERED AN HIV
TEST.
HIV tests occassionally come back “ inconclusive” or “ intermediate” .
This may be due to a false positive (flu shots, lupus, hepatitis, pregnancy
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Dr. Ardis Moe
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etc) or true HIV seroconversion syndrome. Do an HIV RNA PCR (HIV
viral load) and if elevated (usually 100,000 or more), patient is
seroconverting and is infected. If viral load negative, then HIV test is
“ false positive” .
New side effects of HIV meds:
Lipodystrophy syndrome, diabetes, dry skin and mouth, increased risk of
vascular and cardiac disease, multiple drug-drug interactions, elevated
cholesterol and triglycerides.
Nonnucleoside reverse transcriptase inhibitors: delaviridine and efevirenz:
birth defects.
Lactic acidosis: sudden liver failure due to mitochondial shutdown of
respiratory processes. More likely with D4T, DDI although seen with
nevirapine, and all nucleosides. Can occur suddenly after months to years
of nucleoside therapy.
Transmission risks:
Blood transfusion: 100%
Pregnant woman (untreated) and then breastfeeding to baby: 40%
Receptive anal intercourse (person receiving the penis) 1/100 per sex act
IDU—shared needles 1/100 per injection
Needlesticks 1/300 per stick
Pregnant woman (treated—viral load <50 copies throughout 2nd and 3rd
trimester, no breastfeeding) 1% or less
Vaginal sex (HIV+ female to uncircumscised male) 1/250 per sex act
Vaginal sex (HIV+female to circumscised male) 1/1000 per sex act
Vaginal sex (HIV+ male to female) 1/250 per sex act
(HIV viral load major factor in transmission, esp in those groups with
>50,000 copies/ml)
Insertive anal intercouse (person putting in the penis) 1/1000 per sex act
Oral sex 1/10,000 per sex act
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Dr. Ardis Moe
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Presence of herpes or other ulcerative STD’ s may increase transmission
efficiency by 10-100x