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NEUROPATHY:
A COMMON COMPLICATION OF HIV DISEASE
PROMISING
RESULTS FOR PATIENTS WITH
CMV RETINITIS
DIARRHEA
IN HIV INFECTION
OVERVIEW
OF PROPHYLAXIS RECOMMENDATIONS
HIV
INFECTION AND CRYPTOSPORIDIUM
EARLY
DETECTION OF KAPOSI'S RISK
A
NOVEL APPROACH TO CHRONIC DIARRHEA
VISTIDE
FOR RELAPSING CMV RETINITIS
Neuropathy:
A Common Complication of
HIV Disease
By
Daniel S Berger MD
The
prevalence of HIV infection and those on treatment have
increased over recent years and neurologic problems
are among the most common of HIV -related compli-cations.
Antiviral treatment has been linked with toxicity to
peripheral nerves and stage of HIV disease is also associated
with various forms of neuropathy. Additionally, various
opportunistic pathogens, such as cytomegalovirus (CMV)
can directly infect peripheral nerves.
Therefore
an increasing number of patients is being affected by
this neurologic complication and likely to increase;
an understanding of the various forms of HIV-associated
neuropathy and improving treatment options is crucial
for HIV positive patients and their quality-of-life.
There
are various forms of peripheral neuropathy The presentation
can be acute or chronic. HIV neuropathic disease includes
distal symmetric poly-neuropathy, inflammatory demyelinating
polyneuropathy, autonomic neuropathy, progressive polyradiculopathy,
mononeuritis multiplex and diffuse infiltrative lymphocytosis
syndrome.
Distal Symmetric Polyneuropathy
Distal
symmetric polyneuropathy (DSP) is the most commonly
observed form of peripheral nerve complication of HIV
disease. It affects greater than one third of HIV-positive
persons. It occurs in individuals irregardless of specific
T cell number or viral load but in general seems to
be more common among patients with later stage disease.
ItsГ• manifestations include both paresthesias (abnormal
sensations such as numbness and tingling) or aching
of hands and feet in the stocking-glove distribution
and hyperesthesia such as increased sensitivity to walking
barefoot or contact with bed sheets. Other associated
symptoms include numbness, tingling, burning and intermittent
sharp pain in the feet but can also affect fingers of
the upper extremeities.
On
neurologic exam of patients with HIV-related DSP there
is often absent or depressed ankle reflexes relative
to the knees. Other common signs include hyperactivity
of the knee relexes, normal position (proprioception)
, increased vibratory perception and decreased pinprick
and temperature of the stocking glove areas.
Various
mechanisms have been proposed to explain the cause of
DSP. Direct infiltration of HIV in myelinated nerve
fibers of peripheral nerves have been observed, but
not considered likely to be the primary cause. Other
possibilities include vitamin B12 deficiency, cytokines
such as interleukin 1 and tumor necrosis factor, wasting
and malnutrition, and various drugs and neurotoxins.
Antiretroviral
agents have been well documented to demonstrate dose
dependant toxicities to peripheral nerves. Stavudine
(d4T), zalcitabine (ddC) and didanosine (ddI), all of
the nucleoside reverse transcriptase inhibitor class,
are the major drug sources. Additionally, the incidence
increases with further immune system disease. Often
the neuropathic symptoms are reduced with dose reduction
or withdrawal of the offending medication. However clinical
improvement may take several months after these treatment
adjustments.
The
nutritional deficiencies and vitamin components as being
a possible component for neuropathy risk are yet an
additional reason for keeping up with individualГ•s nutritional
status and ensuring that certain vitamins are at optimal
levels for patients on antiviral medications. It is
not uncommon for this author to administer vitamin B12
infections periodically to HIV- positive patients. Other
vitamin supplements that have demonstrated benefit to
improving neuropathy symptoms include other B vitamins,
folic acid and L-carnitine.
Treatment
of DSP is based on symptoms Correcting nutritional deficiencies
and correcting metabolic abnormalities are often useful.
Non-steroidal anti-imflammatory agents, tricyclic anti-depressants
such as amitriptyline, used singly or in combination
are often useful. Amitriptyline is usually started at
low dose of 10 mg nightly and increased gradually, however
anticholinergic side effects and sedation are not uncommon
side effects. Anticonvulsants such as phenytoin(Dilantin),
carbamazepin (Tegratol) and gapapentin (Neurontin) may
also provide relief from symptoms. Recently lamotrigine,
a newer anticonvulsant has shown significant pain reduction
in HIV associated neuropathy. However skin rash is not
uncommon and severe anaphalactoid like reactions have
been reported.
In a placebo controlled trial alternative therapy with
Peptide T has been shown to be ineffective in relieving
pain in DSP. Recombinant human nerve growth factor (rNGF),
effective in treatment for diabetes associated neuropathy
has shown mixed results in clinical trials of HIV infected
patients with DSP .Preliminary studies using acupuncture
as adjunctive treatment for neuropathy has shown some
promise.
Inflammatory
Demyelinating Polyneuropathy
Inflammatory
demyelinating polyneuropathy (IDP) may occur as either
rapidly progressive (acute) or slowly progressive (chronic)
forms. While this is generally an infrequent form of
neuropathy, it tends to occur in asymptomatic HIV infected
individuals but also observed during primary HIV infection
(acute seroconversion). The clinical hallmarks are severe
muscle weakness of two or more extremities but may also
include diaphragmatic muscle involvement in severe cases.
Additional facial weakness, bilateral is also occasionally
seen.
A
lumbar puncture (spinal tap) for cerebrospinal fluid
(CSF) analysis demonstrates a pleocytosis (abnormal
white blood cells) of 10-50 cells/mm3 and protein elevations
of 50-250 mg/dl. In immune devastated individuals, PCR
analysis for CMV DNA may be present. Electrophysiologic
testing is often positive for demyelination.
The
etiology of IDP includes autoimmune mechanism but in
the severely immune compromised, CMV neurologic infection
is often the cause. IDP is primarily treated with immunomodulation
including corticosteroids, high dose intravenous immune
globulin (IVIG) or plasmapheresis. In late stage AIDS,
prompt treatment with aggressive anti-CMV therapy should
be initiated i.e. ganciclovir (Cytovene), foscarnet
or cidofovir (Vistide), alone or in combination.
Autonomic Neuropathy
Autonomic
neuropathy is occasionally observed in HIV-infected
individuals. The autonomic nervous system regulates
many body functions and is devided into two components:
Parasympathetic and Sympathetic. With parasympathetic
involvement, resting tachycardia (increased heart rate),
urinary dysfunction and impotence can be observed. Sympathetic
autonomic dysfunction is characterized by diarrhea,
orthostasis, (light headedness when standing) syncope
(fainting spells)and anhydrosis (decreased sweating)
are noted. Various drugs have been associated with autonomic
dysfunction and include pentamidine, vincristne and
tricyclic antidepressants. Treatment is through management
of signs and symptoms.
Mononeuritis
Multiplex
Mononeuritis
multiplex (MM) occurs in both, individuals with low
CD4 and is usually more severe, as well as in patients
with CD4 counts above 200 count. It is characterized
by asymmetric and proximal involvement (upper part of
arms or legs) of peripheral nerves with tendon reflexes
remaining intact. Sensory and or motor deficits are
both observed in MM and may include cranial or peripheral
nerves. In patients with healthier immune status (CD4
counts > 200 cells/mm3), symptoms resolve spontaneously
or with immunomodulatory therapy within several months.
When occurring in severely immune compromised patients,
nerve involvement is more extensive with rapid progression,
not dissimilar to severe IDP or progressive polyradiculopathy.
Empiric therapy for CMV has been shown to be effective
in treating affected patients with MM.
Progressive
Polyradiculopathy
Progressive
polyradiculopathy (PP) occurs in late stage AIDS, affected
individuals often have a history of prior opportunistic
infections especially CMV end organ disease. It has
a rapidly progressive course if treatment is not administered,
thus prompt diagnosis is key. PP is characterized with
pain and paresthesias (abnormal sensation) in the cauda
equina (lower spine) distribution followed by flaccid
paraparesis (weakenss), loss of reflexes of the lower
extremities, mild sensory deficits and sphincter dysfunction.
Urinary retention is seen in the majority of patients.
If treatment is not initiated mortality rates approach
100% within 4 weeks after the onset of symptoms.
Laboratory testing demonstrate electrophysiologic abnormalities
consistent with lower extremity and lumbar paraspinal
muscle denervation. Cerebrospinal fluid analysis often
reveals elevated white blood cells from 17 to more than
2000 cells/mm3, elevated protein and low glucose levels
below 40 mg/dl. Analysis of CSF for CMV DNA by PCR is
often positive, but aggressive anti-CMV therapy should
not be halted the test for CMV is negative since almost
all autopsied patients with PP demonstrated CMV infection
despite negative serology (testing).
The
etiology of PP points to direct infection by CMV. CMV
has been isolated in CSF, affected nerve routes and
autopsied endothelial, Schwann and ependymal cells in
patients with PP. Additionally, response to prompt anti-CMV
therapy also lends credence to a CMV based etiology
of PP.
Treament
of PP should employ both ganciclovir and foscarnet in
combination. Both agents are capable of passing through
the blood brain barrier. If treatment is initiated early
and prior to nerve root necrosis occurs, clinical improvement
or stabilization can be observed in 50% of affected
patients.
Conclusion
Since
the symptoms of peripheral neuropathy can be debilitating,
effective treatment with appropriate therapy can often
improve the quality-of-life of affected patients. Research
of effective treatment for peripheral neuropathy with
conventional and alternative therapies have not always
shown optimal results. Some of the treatments involve
a trial & error, with stopping or titration of medication
till benefit is reached in each specific patient. Alternative
therapies with acupuncture and massage are sometimes
beneficial, does not involve further pill taking and
is often worthwhile for some patients. Further research
is crucial to improve our understanding of neuropathy
so that more effective treatments become available for
this incapacitating disorder.
PROMISING
RESULTS FOR PATIENTS WITH
CMV RETINITIS
By
Lawrence Stone, MD Stone Eye Center
[Volume
3, Number 1, Jan./Feb. 1997]
Multicenter
trial of an implanted device that delivers ganciclovir
in traocularly for patients with CMV retinitis shows
promising results. In this trial, researchers found
that the median time of retinitis progression was 216
days for implant patients versus 104 days for those
receiving ganciclovir intravenously. The implant, Vitrasert,
containing ganciclovir embedded in a polymer-based system,
is effective for about 8 months, at which time it may
be replaced. The active portion is a pellet which releases
ganciclovir directly into the vitreous cavity The advent
of protease yielding a higher drug concentration than
is possible by intravenous treatment. The procedure
and implant are well tolerated by the patient.
Risk
of the procedure are retinal detachment (about 10%)
which may occur in the first month. It is thought that
the procedure may lead to early posterior vitreous detachment
with subsequent retinal tears and detachment of the
retina. Retinal detachment is also possible in patients
with CMV retinitis on intravenous therapy, although
at a lower rate.
The
field is now rapidly evolving. The advent of protease
inhibitors in our armamentarium seems to have reduced
the number of new CMV retinitis cases. Also, the recent
introduction of cidofovir (Vistide) offers an alternative
to ganciclovir or Foscarnet. Its significantly longer
half life reduces the need for an indwelling catheter.
Induction dosing is once weekly for 2 weeks, with maintenance
dosage every other week thereafter. The treatment requires
the concomitant use of probenicid, which is poorly tolerated
by some patients.
In
addition, there’s the potential for renal toxicity;
3+ proteinurea or a rise in serum creatinine of .5 mg%
are indications to discontinue therapy. The location
of the retinitis and the status of the fellow eye are
important in making treatment recommendations. The presence
or absence of CMV visceral disease, white blood cell
counts, renal status, and potential for drug interactions
are among the many systemic factors which must be weighed.
Consultation between the primary care physician and
an ophthalmologist with experience in CMV retinitis
is important in managing patients with this vision threatening
disorder.
DIARRHEA
IN HIV INFECTION
[Vol.
2, Num. 3, Sept./Oct. 1996 Part 2]
By
Gary Bucher, MD, FAAFP, FACN
The
gastrointestinal tract is a common target for HIV, making
it more susceptible to bacteria, parasites, and viruses.
The last issue of AIDS Infosource, discussed the evaluation
and diagnosis of diarrhea in HIV-positive patients.
Part 2 of this article will focus on various treatment
approaches used in patients with chronic diarrhea, including
pathogen-specific traditional medicine and complimentary
therapies and symptom management with antimotility,
luminal and hormonal agents.
PROTOZOAL
INFECTIONS
Giardia
lamblia is associated with improper food handling, day
care centers and contaminated municipal water supplies.
Diagnosis is confirmed by stool sample or intestinal
biopsy. Giardia may be treated with oral metrondazole
(Flagyl) 250 mg three times a day for five to ten days.
Quinacrine (Atabrine) is also effective for treating
Giardia but was recently banned in the United States.
Alternative treatments include furazolide (Furoxonef)
100 mg. four times daily for 10 days, 2 grams of tinidazole
(Fasigyn) in one dose (not available in the US), and
paromomycin (Humatin).
Paracan-
144 with Artemisia Annua is a combination of grapefruit
seed extract with a Chinese herb. Artemisia Annua is
thought by natural healers and practitioners of Chinese
medicine to be very effective against Giardia. Some
practitioners begin treatment with metronidazole and
then finish treatment with Paracan- 144. Paracidin is
also reported to be effective against Giardia. It is
a combination of three nontoxic compounds: iron sequestering
tannins. fatty acids with broad-spectrum antimicrobial
activity,and absorbed molecular iodine. These compounds
have been reported to be friendly to the normal flora
of the intestine and cause few if any side effects.
Other types of protozoal infections such as Trichomonas
hominis, Dientamoeba fragilis, and Chilomastix mesnili
Cryptosporidiur, it are less common than a most debi
Giardia but can also be leading to is found in the intestine.
They usually do not cause disease in normal hosts. In
is immuno-compromised patients, treated should be initiated
of these I-protozoa if no other underlying cause of
diarrhea is found. ENTAMOEBA INFECTIONS Entamoeba histolytica,
Entamoeba hartmanni, and Entamoeba coli are organisms
that may cause simple self-limh diarrhea or a
syndrome of severe -dysentery. Severe dysentery can
be life threatening if untreated. These are spread by
fecal-oral entshouldbe routes. Metronidazole the seprotozoae
is the treatment of the underlying cause choice as in
giardiasisis found Paromomycin and Iodoquinol 650 mg
three times a day for twenty days is also ) helpful.
Paracan-144 with Artemisia Annua and Paracidin have
been reported to be an effective alternative treatment.
Nonpathogenic organisms like dolimax nana, lodamoeba
butschlii, and Entamoeba polecki usually go untreated
by most physicians. If symptoms persist and these amoebas
are found, treatment should be initiated.
COCCIDIAL
INFECTIONS
Cryptospofidium
parvum causes the most debilitating diarrheal illness
leading to malabsorption and wasting. It can be diagnosed
by stool sample or biopsy. Cryptosproridia caused by
drinking water or spread by other fecal oral routes.
Unfortunately, stool culture and biopsy may miss the
isolation of cryptosoridium. Cryptosproridia infection
is caused by drinking contaminated water or spread by
other fecal-oral routes. There is no definitive treatment
at this time. Treatment includes a trial is of different
agents to see what works for the patient. Paromomycin
750 mg three times a day appears to fiumparvum causes
,debilating illness and absorption wasting. nnance.
be the most effective agent available. If symptoms resolve,
the dose can be reduced for mainte Nitazoxanide (NTZ)
is a new drug in clinical trials for cryptosporidiosis.
It appears to be much more effective than paromomycin
in decreasing symptoms and the amount of organisms in
the stool with fewer pills. Like paromomycin, this is
an intraluminal antibiotic and does i not get absorbed
through the intestinal wall. Though this holds much
promise, it does not get into the gallbladder and biliary
ducts and therefore, cannot clear this reservoir of
infection.
Other
antibiotics that can be tried, but usually have helped
little, include azithromycin, atovoquone, spiramycin,
and diclazuril. Again, what does not work in one patient
may work in another. Hyperimmune milk or colostrum is
a treatment that uses immune globulin that is extracted
from cows that have been vaccinated against Cryptosporidium.
The milk or colostrum is processed so that the immune
globulins are not destroyed. Some reports have noted
markedly decreased secretion of Cryptosporidium in the
stool and even clearance. Clinical trials are currently
underway to test this potential therapy in early infection
before the intestinal wall is severely damaged. Microspora,
Isospora, and Sarcocystis are other coccidial infections.
Recently, cyclospora has also been found to cause a
severe diarrheal illness. Microsporidiosis caused by
Enterocytozoon bieneusi and Septata intestinal is may
be treated with albendazole (Zentel) but may not eradicate
the infection. Other alternative treatments include
metronidazole, azithromycin, clarithromycin, and atovaquone.
isospora, sarcocystis, and cyclospora are treated with
trimethoprim-sulfamethoxazol (Bactrim) with good success.
Blastocystis hominis and Balantidium coli are other
less common causes of diarrhea. These two infections
are treated with metronidazole and tetracycline, respectively.
An alternative treatment for these two infections is
lodoquinol.
VIRAL
INFECTIONS
Cytomegalovirus
(CMV) can cause colitis diagnosed by biopsy of the intestinal
tract. CMV can be detected by special stain, polymerase
chain reaction (PCR) or viral culture. Intravenous ganciclovir
(Cytovene) is the drug of choice for treatment. Induction
doses of 5 mg per kilogram (kg) are given twice a day.
The duration of the treatment depends on clinical improvement.
Foscarnet (Foscovir) is also effective if Ganciclovir
does not work. The dose is 90 mg per kg twice a day
intravenously. After induction therapy with either medication,
maintenance therapy is required to keep the CMV infection
suppressed. Cidofovir (Vistide) was recently approved
for the treatment of CMV retinitis, however, no studies
have been done in CMV colitis. It would seem this may
be a treatment option if Ganciclovir or Foscamet fail.
Other types of viruses like Herpes simplex dadenovirus
have also been implicated in causing diarrhea. Treatment
Acyclovir (Zovirax) should be adequate for herpes. Cidofovir
has activity against Adenovirus but is not approved
at this time for treatment.
BACTERIAL
INFECTIONS
Mycobacterium
avium complex (MAC) can cause systemic infection including
severe diarrhea. This can be diagnosed by stool culture
with special stain or with a blood culture. A multiple
drug regimen of clarithromycin 1000 mg twice a day,
ethambutoI (Myambutol) 1200 mg a day, and/or rifabutin
(Mycobutin) 300 mg per day, and/or clofazamine (Lamprene)
100 mg a day may be used in different combinations to
treat this infection. If symptoms persist after four
weeks of treatment, intravenous amikacin may be added.
These antibiotics should be continued until symptoms
resolve. Lower doses may then be used to keep MAC suppressed.
Clostridium difficulty develops in patients when antibiotic
therapy has altered the normal flora of the intestines
and allowing this organism to overgrow. Therapy consists
of either metronidazole or vancomycin. Acidophilus should
also be taken with these antibiotics to help tiling
list replenish the normal flora of the gut.
SYMPTOMATIC
DIARRHEAL MANAGEMENT
Antimotility
agents could be initiated early in chronic diarrhea.
These agents help prevent dehydration and electrolyte
imbalances. These medications should be taken on a regular
schedule to maximize the effects and stabilize the frequency
and amount of diarrheal episodes. Mild antimotility
agents include Imodium and Lomotil. If these fail to
give adequate control, stronger medications like tincture
of opium, paregoric, or opiates may be used. Luminal
agents can either add fiber or bulk to the stool or
bind bile acids, thereby preventing their conversion
into laxatives by bacteria in the colon. Colestipol
an cholestyramine bind the bile acids in the intestine.
An agent that absorbs the excess water causing less
fluid in the stool is Metamucil. Octreotide (Sandostatin)
is a hormonal agent that is useful in patients with
severe, watery diarrhea. It works by inhibiting the
secretion of fluid into the intestinal lumen. Some patients
respond very well to this treatment.
Diagnosis
and treatment of diartheal illnesses requires patience
and persistence. As hard as it is to diagnose the cause,
it is equally as difficult to find a satisfactory treatment
that is acceptable to the patient. But with a cooperative
team effort, diarrhea can be a chronic but manageable
illness.
OVERVIEW
OF PROPHYLAXIS RECOMMENDATIONS
An
Update from the International AIDS Conference
[Vol. 2, Num. 3 Sept./Oct. 1996]
Vancouver,
B.C. ; July 1996 By Kathleen M Delaney, M.S.
Prophylaxis
against opportunistic infections in the treatment of
HIV disease is a critical element in the care of an
HIV-infected person. The goals of research into prophylaxis
are diverse. For new prophylaxis drugs and regimens,
research must be performed to compare them for effectiveness,
safety, resistance profiles, patient tolerance, interactions
with other drugs, and cost. For prophylaxis regimens
in use now, the standards of care must be fine-tuned
as new results are available. For all types of prophylaxis,
recommendations as to the disease stage at which to
begin prophylaxis must be studied. As the natural history
of HIV is modified by many types of therapy, prophylaxis
recommendations remain in flux. Current prophylaxis
regimens include prophylaxis for PCP, toxoplasmosis,
MAC, tuberculosis, fungal infections, herpes infections,
and CMV retinitis.
Key
questions for research include:
*What
is the most effective prophylaxis for the disease?
What are the side effects of this prophylaxis? What
is the most effective dose? What is the resistance
profile for this drug?
- Do
other drugs being taken affect the effectiveness or
safety of this drug?
- Conversely,
does this drug affect other drugs in the AIDS arsenal?
Interactions
between drugs used to prevent opportunistic infection
and antiretroviral medication is of concern now. When
there is a conflict between these two goals of AIDS
treatment, an individual's physician must examine the
patient's history of disease and treatment to determine
which drugs should be used. The news in prophylaxis
mirrors the news in antiretroviral use: custom treatment
plans for each patient with consideration of the person's
history and conditions by a dedicated and knowledgeable
HIV specialist is the "best practice."At the
Vancouver conference, several sessions on prophylaxis
were presented in composing recommendations and research
results.
One
study whose goal was to compare the effectiveness of
three regimens for MAC prophylaxis also provided some
unexpected results for the prophylaxis of PCP. Studying
the effectiveness of azithromycin for MAC prophylaxis,
results were presented of a study with three arms: azithromycin
1200 mg weekly, rifabutin 300 mg once per day, and a
combination of the two. The study was conducted over
the course of one year. In addition to the MAC results
(azithromycin added to the effectiveness of rifabutin
in the prevention of MAC),
It
was found that the arms who took azithromycin had fewer
cases of PCP. All those in the study were also receiving
standard PCP prophylaxis. Azithromycin reduced the chance
of becoming infected with PCP by 50% in patients with
CD4 < 100. PCP rates were 8.3% in the azithromycin
arm, 8.5% in the azithromycin + rifabutin, and 13.3%
in the rifabutin arm. As there were more than 200 people
in each arm of the study, this result is both clinically
and statistically significant. <Dunne, M.W.> A
recommendation was made for the prophylaxis of TB. Due
to the fact that tuberculosis greatly facilitates the
progress of HIV infection, prophylaxis of TB should
take precedence over any other type of therapy. The
current recommended prophylaxis regimen for tuberculosis
is INH 300 mg per day for 12 months. Even people who
do not test positive for TB exposure, but who are known
to be exposed, in a high-risk group or in a high-risk
environment should be prophylaxes for tuberculosis.
<Reichman, Lee B.>
A
study was performed on HIV positive women to see if
fluconazole 200 mg per week was more effective than
placebo at preventing mucosal candidiasis: vaginal,
oral or esophageal. After following the women for a
median of 29 months, fluconazole was proved more effective
in preventing these types of candidiasis. 27% of those
on fluconazole had at least one episode of candidiasis
during the study, but 45% of those on placebo had at
least one episode. This is also a significant result,
as more than 320 women participated. This was a CPCRA
study at 14 different sites. Drug resistance during
the course of the study was small, and equivalent in
both the active and placebo arms. <Schuman, Paula>
The most effective prophylaxis for PCP also happens
to be both relatively inexpensive and easy-to-take:
TMP/ SMX (Bactrim). The problem with this drug is that
some patients are allergic to it. An important study
was done to evaluate a method for desensitizing patients
to the TMP/SMX by giving them steroid therapy with small
and then increasing doses of the TMP/SMX. As the amount
of TMP/SMX was increased, the prednisone (steroid) therapy
was tapered off. The patient was considered to be successfully
desensitized if at 30, 60, and 90 days, he or she was
tolerating the TMP/SMX without the steroid. In this
study 78% of the 36 patients who entered were successfully
desensitized. This is a very promising result. TMP/SMX
is definitely the preferred PCP prophylaxis regimen,
and it confers a prophylactic benefit against toxoplasmosis
as well. <Beardsell, Ann D.>
There
was an interesting session comparing the cost-effectiveness
and quality-of-life improvement of the different prophylaxis
regimens currently in use. Data from the Multi-Center
AIDS Cohort Study (MACS), other clinical trials, and
results from the AIDS Costs and Services Utilization
Survey were all used to support this analysis. PCP prophylaxis
with TMP/SMX was far and away the most cost-effective,
life-prolonging and quality-of-life enhancing. Actually,
this prophylaxis went beyond cost-effective and generated
true cost savings. MAC prophylaxis with rifabutin was
also cost-effective, though not as dramatically, costing
$200,000 per year of life saved. Fungal and CMV prophylaxis
were much more expensive, at over $2,000,000 per year
of life saved. <Freedberg, Kenneth A.>
HIV
INFECTION AND CRYPTOSPORIDIUM
Cryptosporidium
is a parasite that can cause severe symptoms such as
watery diarrhea, abdominal cramps, fever, nausea and
vomiting. Cryptosporidium is present everywhere in the
environment. Waterborne outbreaks of cryptosporidium
infection have been documented in association with unsafe
drinking water. Therefore, we would like to inform our
patients of the following recommendations to help minimize
the chances of getting cryptosporidium.
1
. Boiling your drinking water for at least two minutes
appears to be the most economical approach to this
problem. The water can then be cooled and stored in
capped containers that have been carefully cleaned
and rinsed with the boiled water.
2.
Use distilled water. You might wish to enhance the
taste of the distilled water with a slice of lemon
or lime.
3.
If you choose to use a water filtration system, make
sure the filter can remove particles as small as half
a micron(O.5um). Most filter systems that use carbon
or sand will not filter out cryptosporidium cysts.
Most reverse osmosis systems that can be installed
in your house are fine. However, the cost can be high
and the system will need regular maintenance and filter
changes to operate properly.
4.
At this time the only brand of bottled water that
advertises that it is "cryptosporidiumfree"
is Sparklett’s (regular or"Crystal-fresh",also
available from Aqua-Vend machines). Bottled water
companies must only adhere to the same testing and
monitoring guidelines as the municipal water supplies.
However,
the Sparkletts Co. claims to use a filtering process
which is sufficient to remove cryptosporidium.To avoid
other exposure risks: the water that you use to make
ice cubes, for washing raw fruits and vegetables, or
for brushing your teeth, should also be boiled or filtered
with the above mentioned systems. When you dine out
in a restaurant, refrain from chewing on ice cubes or
drinking the water. Order tea, coffee or any beverage
that has been boiled. Soft drinks from a bottle or can
are also fine.Other possible sources of infection include
eating uncooked, contaminated produce; drinking water
from a river, pool or lake; drinking unpasteurized dairy
products; sex involving fecal-oral contact; or touching
contaminated soil or infected people or animals without
wearing gloves or washing hands thoroughly afterwards.
Fruits and vegetables to be eaten raw should be washed
thoroughly with soap and water and peeled, if possible.
Early
Detection of KaposiГ•s Risk.
A
new test is being developed to detect the presence of
HHV-8 (herpes virus type 8) the virus believed to be
the cause kaposiГ•s sarcoma in AIDS. Although the incidence
of KS is declined among patients treated with triple
therapy many individuals that are untreated are still
at high risk. The test may be used in addition to other
screening tests for HIV positive patients that may aid
in the decision making of starting on treatment for
HIV.
A
NOVEL APPROACH TO CHRONIC DIARRHEA
The
use of Ultrase MT20 Pancreatic Enzymes for its Effects
on Diarrhea
By Cade Fields-Gardner,
MS, RD/LD
Background
Research
completed over the last few years suggests that much
of the wasting process may not be a necessary
part of the natural history of HIV disease. In other
words, it may not have to happen. We are learning about
the reasons behind wasting and malnutrition in HIV disease
and how to prevent and reverse weight loss. The problems
leading to weight loss and wasting are categorized as
either "starvation" or "metabolic dysfunction."
Much of the research on anabolic therapies are concentrated
on either correcting or indirectly treating for metabolic
changes that lead to weight loss. But in the "starvation"
category, though it seems much more straightforward
than metabolic changes, we still have a battle on our
hands.
Diminished
food intake and absorption are primary factors in weight
loss and wasting in HIV disease. Malabsorption of nutrients
is manifested by a slow weight loss and leads to fatigue.
Sometimes diarrhea accompanies the malabsorption of
fat, lactose, and other nutrients. Though there may
be more than one reason for malabsorptive diarrhea,
problems with pancreatic function may be a common contributor
in HIV disease. Pancreatic enzyme replacement is currently
being explored as a means to treat nutrient malabsorption
and as an adjunct treatment for diarrhea.
Malabsorption
Malabsorption
and decreased nutrient intake are the two major causes
of the low-grade continuous starvation-style weight
loss in HIV disease. High-calorie food plans that are
modified for diarrhea or malabsorption are the usual
recommendation when food intake is diminished. Appetite
stimulants play a major role in increasing nutrient
intake. Research by Macallan's group in England suggested
a two-day window for very poor intake before the more
severe consequences (weight loss and wasting) kick in.
But
for those who are consuming all that they can and still
feel the effects of "starvation"-- loss of
energy and low grade weight loss -- there may be a second
complicating factor: malabsorption. Symptoms that may
indicate malabsorption include diarrhea, abdominal pain,
bloating, fullness, fatigue, and food intolerances.
Malabsorption can happen for a number of reasons, including:
gut pathogens that damage intestinal absorption surface,
changes in stomach acid secretion, changes in intestinal
and pancreatic secretion of enzymes (used to break nutrients
down to absorbable nutrient components), and others.
Obviously, if there is a pathogen (such as cytomegalovirus
or cryptosporidium) it needs to be treated effectively
to return intestinal enzyme production and absorptive
surface back to normal. If there are changes in the
stomach's acid level, alternate nutrients and other
strategies can be used. It makes sense that if pancreatic
production or delivery of enzymes to the intestines
are a factor, pancreatic enzyme replacement may be a
viable treatment.
Pancreatic
Function in Malabsorption
Pancreas
function has been the subject of a good deal of research
in HIV. The pancreas is responsible for a number of
body functions, but affects intestinal absorption primarily
by its provision and delivery of enzymes and bicarbonate
to break down nutrients. A number of events may prevent
the pancreas from fully functioning. Infections with
pathogens (CMV or others), drug toxicity (including
alcohol), or biliary tract disease may limit the pancreatic
enzymes received in the intestines. In other disease
states that share these complications, replacement of
pancreatic enzymes has been successfully used to treat
malabsorption and its accompanying symptoms that often
result. In HIV disease, pancreatic dysfunction may be
low key enough to prevent adequate diagnosis. Clinicians
have been using diarrhea and fat malabsorption (common
complications) as a potential indicator of pancreatic
problems. Pancreatic enzyme therapies have therefore
been suggested as a means to diminish diarrhea and fat
matabsorption. This, in turn, may have additional positive
benefits, such as reducing constitutional symptoms (e.g.,
loss of appetite and fatigue).
About
Pancreatic Enzymes
Prescription
pancreatic enzymes are usually a mix of lipase (to break
down fats), amylase (to break down starches and sugars),
and protease (to break down proteins). Like many medications,
doses may vary according to individual needs. Previous
studies on pancreatic enzymes in HIV disease suggested
an improvement in fat and other nutrient absorption
and a reduction in the volume of diarrhea. Other interesting
findings include an increase in appetite and energy
level.
In
an effort to discover their effect on diarrhea in HIV
disease, the Chicago Center for Special Immunology is
taking part in a multicenter trial on UltraseВ® MT20,
sponsored by Scandipharm, Inc. Inclusion criteria for
the study are HIV status and chronic diarrhea for two
or more weeks. The study lasts for four weeks and requires
a baseline and two follow-up visits. A test for intestinal
absorption (serum d-xylose test) will be conducted during
the study. UltraseВ® MT20 pancreatic enzymes will be
provided free of charge for the duration of the study
and the absorption test will be paid for by Scandipharm,
Inc. The individual may be advised to continue UltraseВ®
MT20 if the treatment improves diarrheaduringthefourweektrial.
Ifyou are interested, please contact the Chicago CSI
office.
VISTIDE
FOR RELAPSING CMV RETINITIS
By
Gary G. Bucher, MD and Daniel S. Berger, MD, FACN
[ Vol. 2, Num. 1, Jan./Feb. 1996]
Cytomegalovirus
(CMV) retinitis is the most common cause of visual problems
in patients with AIDS, occurring in 10 to 30% of AIDS
patients. Retinitis is seen in the majority of patients
with CD4 cell counts less than 100 cells/ut. There are
CMV screening programs which have helped to identify
this condition before symptoms develop. Subjective symptoms
may be subtle such as the presence of ‘floaters"
or profound with sudden vision loss.
Two
drugs have been approved by the FDA to treat CMV retinitis.
Ganciclovir and foscarnet have both been shown to be
effective in delaying disease progression of CMV retinitis.
However, previous studies using these drugs have shown
relapses in a short period of time (median of 76 days).
Both previously approved drugs have significant potential
side effects including bone marrow suppression with
ganciclovir and decreased calcium, magnesium, and possible
kidney problems associated with foscarnet.
New
therapies are being developed to improve patient survival
and quality of life. Implantation of intraocular devices
that slowly release ganciclovir are under study but
are limited in that they treat CMV retinitis but not
systemic CMV. This treatment is associated with a significantly
longer time to progression of retinitis with a median
time of 226 days until retinitis progression. Oral ganciclovir
has been approved for maintenance therapy after initial
treatment with IV ganciclovir. Recently, it has also
been approved for CMV prophylaxis. However, this drug
is poorly absorbed and the time to disease progression
is approximately the same as the IV treatments. This
may be prove to be a viable option when combined with
the intraocular devices.
Intraocular
injections of different antivirals and antisense compounds
are also being investigated. These drugs should add
to the treatment options of CMV retinitis but not concurrent
systemic infection.
A
new drug available through a Treatment Investigational
New Drug (TIND) program is Vistide (cidofovir), formerly
known as HPMPC. This TLND is approved for relapsing
CMV retinitis after use of systemic ganciclovir or foscamet.
This drug has potent activity against viral pathogens
such as CMV, herpes simplex virus types 1 and 2, varicella-zoster
virus (the virus that causes shingles), and EpsteinBarr
virus. In addition, cidofovir (CDV) exhibits activity
against adenovirus and human papilloma virus (HPV).
This
drug has many advantages over the standard CMV treatments.
Infrequent doses are required due to the long half-life
that CDV possesses. No long-term central IV catheters
are required for administration since the drug is given
every two weeks which eliminates the chances of systemic
infections from the catheter.
CDV
is currently in phase III clinical trials for relapsing
CMV retinitis. Interim analysis demonstrated that time
to disease progression was much better than seen with
ganciclovir or foscarnet. The median time to progression
was 115 days as compared to 76 days for the two standard
treatment regimens. This drug is given systemically,
therefore, it may be beneficial for other end-organ
manifestations of CMV disease as well.
The
most common side effects associated with CDV use is
kidney toxicity. Kidney function can be affected and
must be monitored closely. Leakage of protein into the
urine can be an early indicator of kidney inflammation.
Neutropenia or a decrease in the total white blood cell
count is also common. Dose adjustment for CDV can be
made to compensate for the changes in kidney function
and white blood cell count.
Other
less common side effects were listed as mild to moderate.
Most of these reactions were secondary to probenecid,
a drug that is given at that same time as CDV. Probenecid
is given to help prevent kidney damage. These reactions
include fever and chills, rash, nausea, and headache.
These side effects were reversible when the drug was
discontinued.
Cidofovir
appears to be safe and efficacious in treating CMV retinitis.
There is a longer disease free period than that seen
with ganciclovir and foscarnet. Studies are ongoing
at this time. More data must be obtained for cidofovir
to become an FDA approved therapy for CMV disease.
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