|
Warning:
Agenerase, methadone and the Pill
FDA approves once-daily Epivir
For shame
Barebacking
Acupuncture and cocaine
Cost of medicines
WHO: HIV drugs “essential”
News from the XIV International
AIDS Conference
Re-infection: Update
Viread
Viread vs. Zerit
Once-a-day Retrovir
Once-a-day Viramune, Videx and
Viread
Viramune and the liver
Viramune and Kaletra to spare
the nukes
Sustiva beats a dual PI combo
Warning:
Agenerase, methadone and the Pill
The U.S. Food and Drug Administration
(FDA) announced a change in the product label for Agenerase
(amprenavir) HIV protease inhibitor, both the capsules and
the liquid formula. Agenerase might lower blood levels of
methadone. It might also be less effective itself because
of decreased blood levels when taken with methadone. The FDA
reports, “Alternative antiretroviral [HIV] therapy should
be considered. Dosage of methadone may need to be increased
when coadministered with Agenerase.” As for the Pill, “Those
taking Agenerase should be instructed not to use hormonal
contraceptives because some birth control pills (those containing
ethinyl estradiol/norethindrone) have been found to decrease
the concentration of amprenavir. This may lead to loss of
virologic response and possible resistance to Agenerase. Alternative
methods of non-hormonal contraception are recommended.”
FDA approves
once-daily Epivir
Great news: Epivir (lamivudine)
can now be taken once a day. The U.S. Food and Drug Administration
(FDA) in June approved a dose of 300 mg once a day. Once-a-day
and twice-a-day dosing of Epivir was found to be equivalent.
However, the maximum blood concentration was 66% higher and
the minimum level (trough) was 53% lower with the once-daily
dose, although the area under the curve was equivalent with
both doses. (AUC is the total drug concentration between one
dose and the next.) New 300 mg tablets should be available
when you read this. Or, the 150 mg dose, which was taken as
one tablet twice a day, can be taken as two tablets once a
day. Many doctors have been prescibing that dose for years.
Adherence becomes more important with a once-daily dose. People
should make sure they take their dose, or take it as soon
as they remember that they missed it. (But don’t double a
dose—which means you take two doses within a small window
of time from each other.)
For
shame
Ronald Hill, a former San
Francisco health commissioner, was ordered to pay his ex-lover
$5 million for lying about his positive HIV status and exposing
the man to the virus. The former partner later tested positive
for HIV. He told a San Francisco Superior Court commissioner
that Hill repeatedly lied about his HIV status, even after
the partner tested positive. According to court testimony,
Hill, who was appointed to the health commission in 1997,
had claimed his poor health symptoms were a result of cancer.
Criminal charges may follow.
Barebacking
The U.S. Centers for Disease
Control reported that more than a fifth of gay and bisexual
men surveyed who had engaged in unprotected anal sex with
casual partners were HIV-positive. The study, published in
the March issue of AIDS medical journal, found that 38 out
of 554 men said they had barebacked at least once in the previous
two years. Better physical feeling was the most common reason
given for barebacking, followed by “feeling emotionally connected.”
Acupuncture
and cocaine
Acupuncture structured for
treatment of cocaine addiction performed as well as relaxation
techniques and acupuncture not used specifically for addiction.
Researchers from the Yale University School of Medicine put
study participants into one of the three treatments for eight
weeks. Participants received 40 minutes of treatment each
weekday. They were also given access to individual counseling
and allowed to participate in a methadone program. Abstinence
from drug use and satisfaction with treatment received were
about the same in all three groups. All three also had a significant
decrease in the seriousness of their problems with mental
health, the law, family relationships and alcohol. The study
results match anecdotal reports to Positively Aware about
the use of acupuncture for drug users—it does not cure serious
habits. However, it can relieve symptoms of withdrawal. The
study was published in the Journal of the American Medical
Association (JAMA).
Cost
of medicines
“There is a Law: Drugs Don’t
Have to Cost So Much” was the topic of a recent commentary
in the Houston Chronicle. Authors Peter Arno and Michael
Davis severely criticize the U.S. government for not using
the law to lower the costs of medicines produced with taxpayer
money. “Bayh-Dole is a provision of U.S. patent law that states
that practically any new drug invented wholly or in part with
federal funds will be made available to the public at a reasonable
price. If it isn’t, the government can...license it to third
parties that will make the drug available at a reasonable
cost… The American public pumps more than $20 billion a year
in taxpayers funds into health-related research and development,
making it the single largest investor in the pharmaceutical
industry.” The writers state that, “as of 1997, 54 of 84 anti-cancer
drugs approved by the Food and Drug Administration were the
products of federal funding. The percentage is even higher
with respect to AIDS drugs developed with federal funds.”
Visit the U.S. Centers for Disease Control Web site to see
more of the commentary: ftp://ftp.cdcnpin.org/PrevNews/apr02/update041802.txt.
WHO:
HIV drugs “essential”
The World Health Organization
has added almost all of the approved anti-HIV drugs on the
market to its Essential Medicines List, along with treatment
guidelines for poor countries. Previously, only Viramune and
Retrovir were on the list, for the prevention of HIV transmission
from a pregnant woman to her infant. A WHO official told the
Associated Press that the “essential medicines” declaration
could be used to negotiate price reductions with pharmaceutical
companies. In addition, it is hoped that the WHO endorsement
will eliminate questions about safety and effectiveness.
News
from the XIV International AIDS Conference in Barcelona in
July. For more conference news, visit:
• http://hivinsite.ucsf.edu/InSite
• www.aids2002.com
• www.medscape.com
• www.hivandhepatitis.com
• www.kff.org
Re-infection:
Update
Can a positive person infect
another positive person with a new strain of HIV? The idea
of so-called “re-infection” was widely supported by HIV specialists
all over the country, but so difficult to prove with solid
scientific work that it was left in the area of the theoretical.
An earlier report from Toronto of re-infection turned out
to be flawed and therefore out-and-out wrong. But now one
prominent research lab has evidence of a case of re-infection,
and that’s enough to strongly indicate that the phenomenon
really does exist.
Dr. Bruce Walker of Harvard
Medical School had a patient with a blip in his cytotoxic
(“killer”) T-lymphocytes. The patient admitted to having had
an unprotected anonymous sexual encounter. Walker’s HIV lab
documented the existence of another strain of the virus in
the patient’s blood. Previously, his immune response worked
wonders against his original strain of HIV. Now, it failed
to keep the new one under control. This report demonstrates
the importance of maintaining safe sexual practices, even
though both partners are HIV-positive.
Walker’s report came from
his vaccine work, and once again addressed the difficulty
of creating a vaccine that can be effective against multiple
strains of HIV.
Researchers from another lab,
at the University of Geneva, also reported a case of re-infection.
Their patient had a huge rise in viral load. Through sophisticated
work in blood samples, the lab was able to show a new strain
of HIV. They said this strain was one commonly seen in Brazil,
and the patient had taken a trip to Brazil, where he had several
unprotected sexual contacts, three weeks before the viral
load rebound in question. The researchers wrote that this
second strain had a much greater ability to replicate than
his first. They also noted that, “Super-infection [one infection
on top of another] has implications for the ever increasing
HIV-1 genetic diversity, public health, and vaccines development.”
(HIV-1 is the type found in the North, such as the United
States and Europe.)
In his report on this case
for www.Medscape.com,
HIV specialist Dr. W. David Hardy, of Los Angeles, wrote,
“Thus, these investigators have used sophisticated molecular
virology techniques coupled with epidemiologic data to demonstrate
conclusively the occurrence of HIV-1 superinfection in this
patient. Whereas previous reports strongly hinted at this
phenomenon, proof from molecular virology was lacking. The
fact that the two HIV-1 subtypes acquired by this patient
were different subtypes (AE and then B) increases the certainty
that superinfection occurred in this patient. Although this
report holds significant virologic and epidemiologic interest,
its most compelling message is that HIV-1 infected persons
must avoid possibly multidrug-resistant virus. HIV-treating
physicians and treatment advocates should take heed of this
well-documented scientific report to inform their patients
and clients of this phenomenon, and encourage them to observe
safe sex guidelines.”
Viread
How does the relatively-new
kid on the block stack up? Researchers randomized 550 study
participants to take placebo (sugar pill) or Viread for six
months, then everyone took Viread for the other six months.
At six months of study, these heavily pre-treated people had
a little over half-log viral load decrease. This was a significant
reduction, and it remained throughout a year of study. Researchers
for Study 907 concluded that Viread can significantly lower
viral load even in people with extensive HIV drug resistance.
However, because these individuals were heavily pre-treated,
with underlying resistance to HIV meds, only 41% of the participants
went to below 400 viral load, and only 18% to below 50. Side
effects were the same as seen with placebo. Viread is a one-tablet,
once-a-day drug. (See also “What’s
New with Drug Regimens?” in this issue.)
Viread
vs. Zerit
At one year, Viread was as
safe and effective as Zerit when taken in combination with
Epivir and Sustiva. Results are from 600 participants in a
large, randomized clinical trial. All of these Study 903 participants
were taking therapy for the first time. About 87% of all had
less than 400 viral load (95% if you consider only those people
who remained on therapy, rather than counting the people who
dropped out of the trial). A T-cell increase of 150 was seen
with both drugs.
Positively Aware columnist
Dr. Dan Berger, of Chicago, who worked as an investigator
in this trial, notes that the significant increases in cholesterol
and triglycerides in the patients randomized to the Zerit
arm was a very important and surprising finding. He said this
study confirms the safety of Viread while Zerit continues
to demonstrate concern, now in patients being started on treatment
for the first time. Also, his clinic saw no toxicity with
Videx after adding Viread in phase II and III trials or during
early expanded access. There were about 50 patients total.
However, other clinics have seen problems. For example, there
have been cases of pancreatitis when using the two drugs together.
(See “For Experienced Folks”
in this issue.)
Once-a-day
Retrovir
Can you take Retrovir (zidovudine,
AZT) once a day instead of twice a day? A two-week pharmacokinetic
(PK) study looking at blood levels showed a significant viral
load reduction either way (at least a half-log drop for all
32 participants). Further research looking at Retrovir in
drug combinations is needed before recommendations can be
made.
Also, the slope of viral load
decline was smaller for the once daily dose over the 14 days,
but this was not statistically significant. However, in different
analyses comparing different days, the slope was statistically
greater in favor of the twice-a-day dosing.
Moreover, the total viral
load drop was greater in the twice-daily group. Reductions
ranged from 1.067–0.630 log (mean 0.849) in the twice-daily
group. In comparison, the once-a-day group reductions were
0.728–0.442 log (mean 0.585). This was almost a statistically
significant difference (p = 0.056). The usual Retrovir dose
of one 300 mg tablet, twice a day was compared to taking the
two tablets once a day instead.
Once-a-day
Viramune, Videx and Viread
In 65 out of 159 clinical
trial participants who reached 24 weeks of study, all but
two had less than 80 viral load. They were randomized to either
continue their twice-a-day regimens or go on Viramune/ Viread/Videx
once a day (four pills at breakfast time). Researchers concluded
that the once-daily dosing “seems to be equally suppressive”
as standard of care regimens, with improvements in triglyceride
levels and quality of life. However, 10 of the 65 (15%) stopped
therapy: three because of hepatitis, two for rash, one for
neuropathy (nerve damage), one for severe dry mouth and three
did not continue visits. All participants were already on
a HAART (highly active antiretroviral therapy) regimen for
at least nine months when entering the study. They had less
than 80 copies viral load at that time. The Spanish study
is scheduled to continue for three years. No Viramune-associated
liver toxicity or Videx toxicity was seen. Unfortunately,
the report did not state the dosage or formula of Videx that
was used. (See “For Experienced
Folks” in this issue.)
Viramune
and the liver
The manufacturer of Viramune,
Boehringer Ingelheim, presented results of its Viramune Hepatic
Safety Project. To cut to the chase: “In cohort studies, nevirapine
was not associated with a great risk of clinical hepatitis
than other [antivirals].” Also, “The majority of NVP-associated
hepatic events are asymptomatic and easily addressed by NVP
interruption until the ALT/AST (liver function tests) return
to baseline with subsequent reintroduction of NVP on a case-by-case
basis.” Findings were based on data from thousands of people.
Asymptomatic (no symptoms) increases in liver enzymes were
seen in half-a-percent to nine percent of people taking Viramune
in clinical trials, so the risk is greatly individualized.
This study underlies the importance of liver function monitoring,
even though one is asymptomatic.
Viramune
and Kaletra to spare the nukes
Usually, a HAART regimen includes
a backbone of two nucleoside analogs, also called “nukes.”
These include Combivir, Zerit and Epivir. Here, researchers
from Spain and Germany looked at a nucleoside-sparing regimen
of only Viramune (a non-nucleoside analog) and Kaletra (a
protease inhibitor with a small dose of another PI, Norvir,
in each capsule).
The preliminary results of
the small trial: Viramune/Kaletra compared favorably to Kaletra
plus two nukes at six months. However, T-cell increases were
higher in the nuke-sparing regimen—from 552 to 758, compared
to from 640 to 668 in the nuke arm. The regimen consisted
of one Viramune tablet and three Kaletra capsules twice a
day. The 30 participants in this study were already on treatment
for at least nine months before joining. They were already
experiencing cholesterol increases, and this did not revert
with either study arm.
Sustiva
beats a dual PI combo
Sustiva has previously shown
its superiority compared to protease inhibitor (PI) combinations.
Now it beat out the once-daily dual PI combo of Agenerase
with a Norvir mini-dose of 200 mg. Results from a randomized,
open-label trial with almost 300 people who were on therapy
for the first time were presented. Everyone received Ziagen/
Epivir as a base for their combo, and the study’s finding
that these were safe and well-tolerated when used together
is an important advance for HIV therapy. Dr. Brian Boyle reported
for www.hivandhepatitis.com
that, “This [48 week—a statistically significant amount of
time] analysis found that the Sustiva arm significantly outperformed
the other two arms of the study in achieving a viral load
of less than 50 copies/mL. Using an intent to treat, missing
= failure analysis [a high standard], the Sustiva, Agenerase
and Zerit arms of the trial had success rates of 76.3%, 59.4%,
and 62.2%, respectively.
“[For people with] viral load
greater than 100,000 copies, the Sustiva arm also proved superior
to the other arms in achieving viral reduction to less than
400 and less than 50 copies. Finally, grade 2-4 adverse events
occurring in at least 5% of patients were similar for all
treatment arms: 38% for Sustiva patients and 35% each for
Agenerase and Zerit patients… The CLASS study demonstrates
the potency of Sustiva and adds Agenerase to the lengthy list
of protease inhibitors it has outperformed. Further, the study
shows the potential utility of a Ziagen and Epivir regimen,
which appeared to be reasonably well tolerated in combination
with other antiretrovirals.”
|
