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News Briefs: Sep. - Oct.
2000
by Enid Vázquez
Subjects:
Children
Pregnancy
Stop
Ziagen kills
Social Security
New protease inhibitor
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News from the 13th International
AIDS Conference, July 9-14, Durban, South Africa
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Children
The National Cancer
Institute reported a very high rate of cancer in children
with HIV–2.5% (124 out of 4,954 children whose records
were reviewed). But a doctor in the audience noted that the
figure was much higher—four times more—than was
seen in any other published report, and noted that when he
and other researchers looked at cases of cancer in HIV positive
children, the majority of the cancer diagnoses could not be
confirmed.
Other U.S. researchers noted
that with improved HIV therapies, there will be greater concern
over the potential for pain and other quality of life problems
in people living with the virus, but that no one has looked
at pain in children. PACTG 219 (Pediatric AIDS Clinical Trials
Group) found in a survey that children with a CD4 percentage
of less than 15% (severely immune suppressed) were almost
three times more likely to report pain. (In children, CD4
percentage is more important than T-cell counts.) Overall,
20% (one in five) of the children experienced pain. The research
is important because adults are frequently unable to notice
pain in children.
A big question: do children
born to mothers on HIV drugs get hurt by the medications?
Most research shows that they don’t. But researchers
from the Netherlands reported immune system damage and blood
cell malfunctions (such as much less CD4 T-cells) in negative
children of positive moms. The report started a storm of controversy
in the audience. Among the issues raised was the fact that
this was a one-time look at the umbilical cord blood at birth;
the researchers are still looking at how fast the children’s
immune system recovers; and that these may be transient problems
(the presenter said they will look at that).
Brazilian researchers found
a high level of blood lipid changes (51%) in children and
adolescents on anti-HIV drugs (as is found in adults). Those
with a longer history of symptomatic disease had a greater
risk of lipid problems (more cholesterol or triglycerides,
a type of fat). Actual changes in physical appearance was
greater in the kids taking a protease inhibitor (five out
of 29, compared to one out of 37 using only two nucleoside
analogues—such as Zerit and Epivir). “Protease inhibitors
seem to play a significant role in the development of abnormal
body fat distribution,” the presenter said.
Researchers reported good
preliminary results in children, even those who previously
took medications (a group that tends to show less benefit),
with the newest protease inhibitor, lopinavir (formerly known
as ABT-378/r), expected to be approved by the FDA (Food and
Drug Administration) soon. After four months, undetectable
viral load (less than 400) was seen in 57% of kids who had
previously taken a protease inhibitor, 77% of kids who had
taken a nucleoside analog, and 79% of kids who had never taken
anti-HIV therapy before. The children’s starting viral
load was not given. The PI-experienced children received Viramune
in addition to lopinavir and two nucleoside analogs. A doctor
in the audience said that much higher doses of the manufacturer’s
current protease inhibitor, Norvir, had to be used in infants
because the company didn’t have enough research to provide
adequate pharmocokinetics (how the drug works in the blood)
in that population. He cautioned that since very few children
here were less than two years old, and only one was less than
six months old, the pharmacokinetic data may again end up
being different once the drug is on the market. In response
to a question, the presenter said the drug is not very palatable
(tasty), but can be easily masked and that children, who are
now a year into the study, no longer complain about taste.
Mexican researchers
found good results with the use of the cancer drug hydroxyurea
(Hydrea) in 24 children. They had greater weight gain, growth,
increases in T-cells and CD4 percentages, less viral load
and less disease after nine months on hydroxyurea (30 mg/kg
a day) with Videx and Zerit. The researchers reported good
tolerance (plus, no cases of pancreatitis) and noted the lower
cost of using hydroxyurea than using one of the potent HIV
drugs, an issue raised by other doctors at the conference
in terms of adult therapy.
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Pregnancy
The most exciting news
for preventing transmission from mother to child came from
a study finding that three doses of Viramune (nevirapine)
was similar to a more expensive and inconvenient combination
of AZT with Epivir. (In the U.S., AZT monotherapy is minimum
standard of care for preventing transmission, but at least
a triple drug combination is preferred, both because it’s
a higher standard of care for the mother and because it reduces
transmission more effectively than just using AZT.) In the
SAINT Study (South African Intrapartum Nevirapine Trial),
more than 1,000 pregnant women were given therapy while in
labor. They received either one tablet of Viramune during
labor and one tablet within 24ß48 hours of giving birth
(with the babies receiving a single 6 mg dose of Viramune
within 24ß48 hours of birth), or the women were given
a 600 mg dose of AZT upon entering labor, with 300 mg every
three hours thereafter, plus Epivir twice a day during labor,
and then both drugs twice a day for seven days after birth
(with the babies getting 12 mg AZT and 6 mg Epivir twice a
day, also for seven days). There were no serious drug-related
side effects. There was a 7% transmission at birth, which
increased 42 weeks after birth to 13.3% for Viramune and 10.2%
for AZT/Epivir (no statistical difference). Forty percent
of the mothers breastfed, although they were offered infant
formula at cost. The findings caused a stir of excitement
among delegates, especially those from developing countries—including
the doctors, because of the ease and inexpensiveness of the
highly effective Viramune regimen (a total of less than $10
for the three doses).
Also comparing well with
AZT in short-course therapy was Zerit, Videx and a combination
of Zerit/Videx. (Short-courses are studied in an attempt to
decrease the cost of the original, longer U.S. trial with
AZT that set the standard for preventing transmission.) In
this study (also in South Africa), the drugs were given from
the 34–36th week of pregnancy, but not during labor.
The drugs were also given to the infants for the first six
weeks of life. Baby formula was provided. Overall, there was
a 3.6% transmission in more than 200 babies. Researchers said
all drugs were safe and well-tolerated, and the “d”drugs
(Zerit is d4T and Videx is ddI) had as much anti-HIV activity
and decreases in transmission as did AZT. There were almost
no drug related side effects.
In another study, breastfeeding
was found to negate the benefits of AZT. In an analysis of
two clinical trials that used short-course AZT in the sub-Saharan
countries of Cote d’Ivoire and Burkina-Faso, there was
no statistical difference in transmission at 24 months after
birth between the women who used AZT (9.4%) and those who
were given placebo (fake drug, 8.6%). Researchers noted that
women with greater HIV viral load (the amount of virus in
their blood) had a greater risk of transmission. It is preferrable
for HIV positive mothers to breastfeed in developing countries
if the families have no access to infant formula or clean
water.
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Stop
German researchers
took a small group of people off their meds for four to six
weeks, then back on for six months. In the group with less
than 50 viral load (HIV in the blood, considered undetectable
here), only 58% were again undetectable after six months.
Overall, they had a median rise of 0.4 log in viral load,
which is statistically significant (not good). During the
interruption itself, the increase was a scary 2.4 logs. They
also lost an average of 11 T-cells at the end of six months.
However, their lipid profile improved. They had lowered their
triglyceride and cholesterol levels.
In the U.S., four people
were put through three cycles of interruption, with four weeks
on therapy followed by four weeks off. All started out with
undetectable viral loads (considered under 400, in this case)
and more than 400 T-cells. After 20 weeks, two of them did
not show an increase to above undetectable (called “rebound”)
after one interruption, but did after the second and third
(for a maximum of 14,000 and 25,000 viral load). The other
two had a rebound during all three interruptions, with a maximum
of 86,000 and 135,000. Viral load came back down with therapy
for all four people, but not always to undetectable.
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following News Briefs are not from the International AIDS Conference. |
Ziagen kills
It's pretty well known that
an allergic reaction to Ziagen (abacavir) can be fatal if
people stop taking the drug and then go back on it. Recently
the manufacturer had to add previously unrecognized symptoms
of hypersensitivity (respiratory problems) to the drug's warning
label. But now the warning has been strengthened. Allergic
reactions either were not being recognized or mistaken for
other conditions, and people have died as a result when they
started taking Ziagen again after an interruption. Sometimes
the interruption had nothing to do with a reaction to the
drug, as when someone stops taking anti-viral medications
while another condition is brought under control. And if that
person or the doctor didn't recognize a hypersensitivity reaction
before, or took it for something else, like bronchitis or
pneumonia—well, you see the problem. The person goes
back on the drug and, usually within hours, suffers a severe
or even fatal reaction. Once again, respiratory warning signs
include cough, difficulty breathing and sore throat. Other
warning signs are fever, fatigue or malaise (overall ill feeling,
as with a flu), and gastrointestinal symptoms (nausea, vomiting,
diarrhea or stomach pain). Rash is sometimes, but not always,
a symptom. For more information, call the Glaxo Wellcome Customer
Response Center tollfree at (1-888) TALK2GW (825-5249).
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Social Security
New changes for people who
work begin in September. The following is from a press release
issued by the Social Security Administration (visit www.ssa.gov/pressoffice/ADA.htm).
The “substantial gainful activity” (SGA) level will
be raised for the first time ever, based on any annual increases
in the national average wage index. (Blindness is excluded.)
Currently, the SGA is monthly earnings of $700 or more, at
which point people are ineligible to continue receiving benefits.
Minimum monthly earnings for a Trial Work Period (TWP) go
up from $200 to $530, and maybe more later on (also based
on the wage index). The maximum monthly earned income exclusion
for students receiving Supplemental Security Income (SSI)
will increase from $400 to $1,290, and the yearly exclusion
increases from $1,620 to $5,200.
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New protease inhibitor
The newest protease inhibitor
may be in pharmacies soon. Lopinavir (formerly known as ABT-378/r)
was recently submitted for FDA approval. Each capsule includes
a small amount of the manufacturer's current protease inhibitor,
Norvir (ritonavir). The brand name is Kaletra. A previously
reported brand name was rejected because it was too close
to that of an existing drug. The FDA doesn't like this because
people have died after getting the wrong drug when the correct
name was misread on a prescription.
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