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Drug
warning
A recently reported HIV drug
side effect, severe muscular weakness, has been associated
with several deaths. This neuromuscular toxicity (NT) is related
to other conditions already recognized as a risk of therapy:
lactic acidosis (LA), pancreatitis, liver damage and mitochondrial
toxicity (cell damage). The condition mimics another disease,
Guillain-Barré syndrome (GBS). The U.S. Food and Drug Administration
(FDA) found seven deaths among 25 cases of serious LA and
NT reported last year (28%). Of the 25, 18 people continued
their drugs despite symptoms, including six of the seven who
died.
Although increased lactic
acid level with HIV treatment is relatively common, there
are usually no symptoms or serious problems. Serious side
effects are obviously rare, but people living with HIV and
health care providers should be aware of them. The number
of severe cases and the deaths were greater among women. Last
year, five cases of profound motor weakness were reported
to the FDA. Also, in 2000, two pregnant women and one fetus
died as a result of lactic acidosis and liver damage (hepatotoxicity)
during a clinical trial.
In a search of its Adverse
Event Reporting System (AERS), the FDA found that 24 of the
25 patients were hospitalized, and 12 of the 25 cases were
women. Of the seven people who died, six were women. The vast
majority, 22, were taking a medical regimen that included
Zerit (stavudine, d4T). “Although a voluntary AERS clearly
has limitations, profound motor weakness that resembles GBS
can be a manifestation of LA,” the FDA reported.
There were eight pregnant
women who developed pancreatitis and/or LA by the eight month
of pregnancy, and seven of them (88%) were taking medications
that included Zerit and Videx (didanosine, ddI). Taking the
two together is known to increase the risk of pancreatitis,
liver failure and peripheral neuropathy. Three of those women
died. The eighth woman was taking Zerit and Epivir (3TC).
There were three fetal deaths, including one in the woman
on Zerit/Epivir. The FDA concluded that, “The risk appears
to be greatest in the third trimester and with longer duration
of ddI/d4T therapy [on average, more than two years for these
eight women]. The combination of ddI/d4T should be given only
to those pregnant women in whom the potential benefits clearly
outweigh the risks.”
Zerit’s manufacturer, Bristol-Myers
Squibb (BMS), sent a letter to health care providers warning
them about the potentially fatal neuromuscular reaction. BMS
stated that Zerit should be stopped in people who develop
muscle weakness or suspected cases of lactic acidosis with
or without muscle weakness. The drug should never be taken
again in people who have confirmed lactic acidosis. In its
letter, BMS noted that, “The early signs and symptoms of clinical
events associated with hyperlactatemia should receive careful
attention because of the life-threatening potential of the
most extreme manifestation, lactic acidosis syndrome (LAS).”
BMS also laid out a number
of symptoms to consider. “Confirmed elevations of serum lactate
may be associated with a broad spectrum of clinical manifestations,
ranging from asymptomatic hyperlactatemia [in other words,
there are no symptoms, and these cases in fact are not a problem],
through symptomatic non-acidotic hyperlactatemia (SHL), to
acute severe LAS [lactic acidosis syndrome]. Early signs and
symptoms associated with a high lactate may be subtle and
include generalized fatigue, digestive symptoms (nausea, vomiting,
abdominal pain, and sudden unexplained weight loss), respiratory
symptoms (tachypnea [rapid breathing] and dyspnea [breathlessness
or difficulty breathing]), or neurologic symptoms (including
motor weakness)… It is important to note that symptoms associated
with hyperlactatemia may continue or worsen following discontinuation
of antiretroviral [HIV] treatment. At this time, prospective
monitoring of lactate levels does not appear to be helpful
in predicting the subsequent occurrence of SHL or LAS.”
In the medical journal Clinical
Infectious Diseases earlier this year, Spanish doctors
discussed 12 cases of unexplained lactic acidosis out of 5,400
HIV positive people on therapy, as well as a review of other
reports (60 cases). Again, women made up about half of all
cases. Of the 12, four died (33%). In the 60 cases, 57% died.
Age and CD4 count did not correlate with death, but having
a serum (blood) lactate level above 10mM was strongly associated
with death. Among seven of the 12 who were given riboflavin,
with or without thiamine, only one patient died. In the literature
review, three out of 11 people treated with these nutritional
supplements died, a smaller percent than seen with the larger
group of 60. The researchers recommended the use of thiamine
and riboflavin for treatment of severe cases, because there
was almost no potential for toxicity seen with them. L-carinitine,
vitamin C and other antioxidants can also be used. As for
Zerit, the number of cases only increased as use of the drug
increased. The most commonly used nucleoside analog before
1996 was Retrovir (zidovudine, AZT), and it accounted for
most of the LA cases before 1996. However, the number of cases
reported from 1991–1996 was 23, all but one of them were users
of Retrovir. In 2000–2001 alone there were 34 cases, 33 of
them were Zerit users. Possibly some of these cases include
people who were previously on Retrovir.
If experiencing symptoms
of lactic acidosis, make sure your blood is drawn without
use of a tourniquet or making a fist. Be well rested too—don’t
take the stairs. There are no tests for mitochondrial toxicity
available in clinics.
Clarification:
hep B virus
News
Briefs in the last issue discussed preliminary findings
of the effectiveness of both Viread and adefovir against resistant
virus in people co-infected with HIV and hepatitis B. To clarify,
the resistance discussed was in the hepatitis B virus of the
study participants, not their HIV.
Combivir
mix-up
Check your med! Combivir
maker GlaxoSmithKline received four reports of Combivir bottles
that contained instead Ziagen, another of their HIV medications.
Anyone who’s previously ever had an allergic (hypersensitivity)
reaction to Ziagen or Trizivir (you know, it’s Combivir plus
Ziagen in one tablet) cannot take either of the two meds ever
again. GlaxoSmithKline alerted pharmacists, physicians and
patients to immediately examine the contents of every Combivir
bottle. Combivir is a white capsule-shaped tablet engraved
with “GX FC3” on one side; the other side of the tablet is
plain. Ziagen is a yellow capsule-shaped tablet engraved with
“GX 623” on one face; the other side is plain. The company
found that in two of the cases, Combivir labels were put on
Ziagen bottles.
Videx-EC/Viread
combo
A new warning to doctors
dated May 7 notes that the potential side effects of Videx-EC
(ddI) may be increased by use of Viread. Serious side effects
of Videx and Videx-EC (the time-release formula) include pancreatitis
and peripheral neuropathy. When both medications were taken
on an empty stomach two hours apart, Videx-EC levels went
up by 46%. But if the Videx-EC and the Viread were taken together
with a light meal (not explained), the Videx-EC levels went
up by 60%. It is not clear yet as to whether dosing changes
of Videx-EC should be made because of the increased blood
levels and it is not yet clear whether these findings will
result in increased potential for side effects. As always
for any HIV meds, monitoring for side effects is urged for
people with both Videx or Videx-EC and Viread in their HIV
combination.
Gay
men: get tested
The U.S. Centers for Disease
Control and Prevention (CDC) recently updated its Sexually
Transmitted Diseases Treatment Guidelines. For the first time,
the CDC recommends that sexually active men who have sex with
men (MSM) get tested for HIV once a year. Moreover, they should
also be annually screened for syphilis, gonorrhea and chlamydia.
Those who have had receptive oral sex should have a throat
culture taken for gonorrhea. Those who have had receptive
anal intercourse should be tested for rectal gonorrhea and
chlamydia. Plus, all MSM should be vaccinated against hepatitis
A and B (there is no vaccine for hep C). The guidelines were
published in the May 10 issue of the CDC’s Morbidity and
Mortality Weekly Report.
Surgical
risk for women
A comparison between HIV
positive women and HIV negative women found the risk of post-surgical
complications to be significantly higher among the positive
women. Researchers looked at the records of 470 women who
underwent obstetric and gynecological procedures. The greatest
difference was in fever lasting more than 48 hours that required
treatment with antibiotics. Lower T-cell counts increased
risk of complications. A fever is one indication of infection.
The study was published by Grubert et al. in Clinical Infectious
Diseases.
Fauci
wins prestigious award
HIV researcher Dr. Anthony
S. Fauci in March was awarded the largest prize for medicine
in the United States, the Albany Medical Center Prize in Medicine
and Biomedical Research, a $500,000 research award. Fauci
is director of the National Institute of Allergy and Infectious
Diseases (NIAID), one of the National Institutes of Health
(NIH), and the one that oversees HIV/AIDS research. He also
became prominent in the fight against threats of bioterrorism
after 9/11. Fauci said part of the award will be used on a
trip to Africa to investigate ways to combat the global epidemic.
Children’s
confidants
According to a report from
the British Broadcasting Corporation, a three-year study of
Scottish children with HIV positive parents found they had
no one to talk to about their fears and concerns. Children
told researchers representing the agency Children in Scotland
that they could not talk with parents for fear of upsetting
them, nor to adults at school out of discretion. They also
reported that they were not given the chance to talk with
health care providers.
Genetic
defects in baby monkeys
A report in the April 1st
issue of the Journal of Acquired Immune Deficiency Syndrome
(JAIDS) noted a greater risk of genetic defects in fetal monkeys
exposed to both Retrovir (zidovudine or AZT) and Epivir than
to those exposed only to Retrovir. (The two medications are
also available in one drug, called Combivir.) However, defects
have not been noted in children exposed to the medications.
Nevertheless, the researchers noted the need for long-term
follow-up of these children (a desire expressed by doctors
for all children exposed to HIV antivirals before birth).
Also, the combination of the two drugs was more effective
at reducing transmission of the virus to the baby monkeys.
Hep
C, cotton and cookers
Hepatitis C virus is easier
to transmit than HIV, and it can be deadly. Like HIV, it’s
transmitted through blood contact. An estimated 80% of people
with a history of injection drug use have HCV. As with HIV,
people need to be careful about sharing drug supplies other
than the syringe. In a recent study, University of Illinois
researchers confirmed the risk of acquiring HCV through injection
equipment. After subtracting the risk of infection through
syringe sharing, the researchers said that sharing “cookers,”
something used to melt down drugs to allow it to be sucked
up by a syringe, increased the risk of getting HCV by four
times. Just sharing the cotton used to filter out impurities
in drugs doubled the risk of HCV. The study was published
in the April issue of the American Journal of Epidemiology.
The report was based on 702 drug users, between the years
1997 and 1999.
HIV
blame
Of people surveyed in the
late 1990s, about 25% said they would feel uncomfortable being
in contact with someone with HIV, 20% had a fear of people
with AIDS, and almost a third said they would avoid their
local grocery store if the owner had AIDS. Researchers reported
that education campaigns have been effective at explaining
how HIV is transmitted and promoting individual responsibility,
but not so effective at stressing the lack of transmission
through casual contact. They also believed the campaigns hurt
people with HIV without meaning to by leading the public to
blame them for their infections, due to the stress on individual
decision-making in sexual contact. Gregory M. Herek and colleagues
reported their findings in the American Journal of Public
Health.
Pap/HPV
guidelines
A panel of gynecological
experts recently created new guidelines for following up inconclusive
Pap smears. Previously, women could have the Pap smear re-done,
have a colposcopy (a look through a microscope) and painless
biopsy taken of their cervix, or be tested for human papillomavirus
(HPV), some strains of which have been associated with cervical
cancer. The recommendation now is to simply test for the presence
of the most dangerous form of HPV, which can be done at the
time of the Pap smear. The change saves time, trouble, and
money, and can relieve anxiety. The guidelines appeared in
the April 24 issue of the Journal of the American Medical
Association (JAMA).
Risky
Behavior in San Francisco
This year, HIV infections
hit a high the city hasn’t seen in 20 years. And once again,
Dr. Mitchell H. Katz and colleagues reported on the continued
practice of unprotected sex in the gay community. Thanks to
HAART (highly active antiretroviral therapy), men say they
are less worried about getting infected, and positive men
are less concerned about infecting others. One result was
a decrease in condom usage. The research results come from
a review of surveys conducted in various public places, such
as bars or on the street. The report was published in the
March issue of the American Journal of Public Health.
Breasts
in men
The development of breasts
in men (gynecomastia) has been seen with the use of HIV medications.
Nelson Vergel of PoWeR (Program for Wellness Restoration)
has found a pharmacy that sells compounded DHT, a treatment
that has been successfully used for gynecomastia. A doctor’s
prescription should be written as “testosterone topical gel
10%, dispense 60 grams.” Cost is $36 plus $15 for shipping
and handling. Mail to Gulfsouth Pharmacy, 3207 International
Drive, Suite C, Mobile, AL 36606. The phone number is 1-877-729-1015.
Vergel also found this description of DHT used in gynecomastia
from MedScape.com,
written by Dr. William G. Powderly, the principal investigator
at the Washington University AIDS Clinical Trials Unit, in
St. Louis. “It is important to exclude other causes of gynecomastia
(e.g., renal disease, liver disease, tumors with increased
estrogen, inhibitors of testosterone, and other drugs) before
attributing the condition to antiretroviral therapy…An intriguing
recent report studied the use of dihydrotestosterone gel applied
to the skin…A total of four patients were treated with dihydrotestosterone
gel, which has an anti-estrogen effect, and all had rapid
and dramatic reductions in breast tissue within 10 to 21 days…the
interesting response to dihydrotestosterone does suggest that
other androgens or anti-estrogens might be beneficial, and
other trials are certainly warranted.” Dr. Dan Berger often
prescribes tamoxiphen at 10 mg per day, an anti-estrogen in
pill form, for the treatment of gynecomastia when due to hormonal
imbalance in HIV positive individuals. In some weight training
circles, individuals who take high dose steroids for anabolism
and weight training have even used this agent to prevent the
onset of gynecomastia. [See “The
Buzz” by Dr. Berger in the Nov./Dec. 2001 issue of Positively
Aware.]
Annual
ADAP report
The National Alliance of
State and Territorial AIDS Directors, the Kaiser Family Foundation
and the AIDS Treatment Data Network recently released a number
of new reports and fact sheets on states’ AIDS Drug Assistance
Programs, which use federal funds to provide prescription
drugs for uninsured and low-income individuals with HIV/AIDS.
Among the findings: 10 states or territories reported having
one or more ADAP restrictions, including capped enrollment,
limited antiretroviral access or expenditure caps. Among the
reports: ways for states to control the costs of ADAP. Visit
www.nastad.org.
Creator
of Red Ribbon dies
Frank C. Moore II, a prominent
Manhattan painter who created the AIDS red ribbon, died in
April of complications due to AIDS, at the age of 48. Moore
was a board member of Visual AIDS, a Manhattan-based group
that raises money to fund artists with HIV/AIDS and helps
maintain the art of people living with the virus. His work
is found in the collections at the Museum of Modern Art and
the Whitney. “Between Life & Death,” a book about his
work, was published this year.
Nkosi
Johnson Honored with Children’s Nobel Prize
He was one of the world’s
littlest AIDS activists. At the International AIDS Conference
in Durban, South Africa two years ago, 11-year-old Nkosi Johnson
spoke at the opening ceremonies, pleading with his government
to provide access to HIV medications to pregnant women in
order to prevent transmission to their child, as had happened
with him. He died a year later. In April, the Swedish organization
The Children’s World recognized Nkosi’s contributions with
a Children’s Nobel Prize. Together with his foster mother,
Nkosi had established a home for impoverished HIV positive
women and their children. The Children’s World called Nkosi
a “role model for children with AIDS and for the healthy children
whom he taught not to be afraid of children with HIV/AIDS
and to respect them.” To make donations to Nkosi’s Haven,
visit http://nkosi.iafrica.com.
South
African doctors: treat pregnancy now
Once again, South African
physicians urge their government leaders to make HIV treatment
of positive pregnant women a reality. In a letter to the British
medical journal The Lancet, the Southern African HIV Clinicians
Society lists strong scientific data supporting the need for,
and use of, HIV medications for preventing transmission to
unborn children. The doctors cited Retrovir (zidovudine or
AZT) and Viramune (nevirapine) as particularly beneficial
and cost-effective. They said Viramune would be beneficial
even if it was 42 times more toxic than what was seen in clinical
trials. Around the time the letter appeared, AIDS activists
in the country organized a march leading nearly 5,000 people
to protest the government’s appeal of a court decision forcing
it to provide Viramune to prevent mother-to-infant transmission
of HIV.
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