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Past Issues
Volume 16, number 10
October 2002
Contents
Face to Face with Zerit's Record
The evidence mounts against a popular HIV drug
I Love My Liver
Staying alive requires persistence and luck
Botswana Responds
Putting the pieces in place to treat everyone
Facts are Funny Things
TI reviews drug fact sheets
Short Course
Notes on drugs in development
Global Treatment Update
Global Fund off to sluggish start
New Liver, Same Spleen
Larry Kramer warns of a coming healthcare disaster
The
Case Against Zerit
By Bob Huff
HIV drug therapy works against HIV. This is clear from the dramatic
drop in deaths due to AIDS after the use of combination therapy
was widely adopted in 1996. But these drugs also act on the body
and its metabolism in a number of strange and hard-to-pin-down ways.
In some people — but not all — blood lipids soar to
alarming levels that are associated with a higher risk of cardiovascular
disease. Yet the rates of heart attack and heart disease in people
taking HIV drugs continues to run about the same as those for people
without HIV. Antiretroviral therapy may make for some worrisome
lab tests, but stopping smoking rather than stopping meds remains
a better bet for keeping a healthy heart.
In some people — but not all — fat deposits in the
arms, legs and, most visibly, in the face, melt away, leaving people
who experience this fat depletion syndrome bearing the tribal scars
of facial wasting. When the fat drains from the face, it may be
very hard to recover. One option for treating this condition is
to undergo an expensive restoration process of soft tissue augmentation
using a filler material injected under the skin of the cheeks.
In some people — but not all — the fat that disappears
from their faces and thighs seems to end up in their belly as waist
sizes bloom. This isn't really what happens, though, and the type
of fat that fills the abdomen, called visceral fat, has different
qualities from the subcutaneous fat lost from the face and limbs.
And not everyone who gains visceral fat loses subcutaneous fat.
And in some people — but not all — insulin tolerance
goes out of whack, which may or may not lead to diabetes. (We won't
even discuss bone formation problems.)
If you notice a pattern here, it's that what seems to be a definable
lipodystrophy syndrome at the 35,000-foot level, becomes a wilderness
of associations and anecdotes once you're on the ground. Inconsistent
methods, unvalidated measurements and tiny studies make simply defining
this complication contentious as researchers continue to tease out
the links between suspected drugs, genetics and HIV itself. So far,
no smoking gun has been found and none is expected to turn up. This
is, as they say, a multifactorial problem. Scientists looking for
answers to this riddle are developing new and more specific lab
tests as well as larger and more reliable clinical trials. And clinicians
are looking at everything from nuke-sparing regimens to prophylactic
glitazones to forestall or minimize the consequences of lipodystrophy.
In the meantime, managing the drug-related toxicities of HIV therapy
remains an art.
Workers in this ad hoc field recently met in San Diego at the 4th
International Workshop on Adverse Drug Reactions and Lipodystrophy
in HIV to trade notes and argue over epidemiology and favorite pathogenesis
theories. For those seeking more than a tantalizing intellectual
exercise, there was little to write home about.
Zeroing In on Zerit
But the weight may be starting to shift on one lingering dispute.
For a long time, whenever talk turned to speculation about which
drugs were considered prime suspects for causing lipodystrophy,
the name of one culprit always came up: Zerit (d4T or stavudine)
is a popular nucleoside analog often combined with ddI or 3TC as
part of a three-drug combination. The federal HIV treatment guidelines
list d4T among its "strongly recommended" choices for
first line therapy. Zerit was linked early on with the nerve damage
that causes peripheral neuropathy in some people. More recently
it's been indicted for contributing to some of the other unpleasant
toxicities of ART, such as facial wasting. Of course, a lot of the
charges were stimulated by studies and presentations funded by GlaxoSmithKline
— makers of AZT and 3TC — who'd love to see this competitor
sent away. And most of the counter-arguments and obfuscation originated
with Bristol Myers Squibb, the makers of d4T. So, although many
people were resolutely convinced of d4T's guilt, controversy held
consensus at bay. But this contest may finally be coming to a head
— if not a verdict — as the evidence against d4T solidifies.
After data presented this year at the annual Retrovirus Conference,
at the International AIDS Conference in Barcelona, and now at the
Lipodystrophy Workshop and the annual ICAAC conference that followed
it a few days later, the strength of the associations between d4T
and fat wasting are becoming too strong to ignore. As one observer
put it, "You can't really say it's just a Glaxo thing anymore."
Mitochondrial Toxicity
The protease inhibitors were the first drug class to take the blame
for fat redistribution and lipodystrophy and evidence continues
to mount against some of them. But nucleoside analogs have also
received scrutiny for their potential to deplete the energy-producing
capacity of cells.
The prevailing theory of how nucleoside analogs contribute to fat
wasting and elevated lipids revolves around a pathogenic piñata
called mitochondrial toxicity. Cellular respiration is the name
for a long series of chemical steps in which cells process glucose
and oxygen into a useable form of energy. If any of these steps
are slowed down or blocked, the whole process backs up and a kind
of overflow system starts to consume glucose without oxygen, which
dumps a byproduct called lactate into the blood. As an extreme example
of what can go wrong with this system, a poison like cyanide can
stop cellular respiration dead in its tracks — with rapidly
fatal results. But the toxicities thought to be caused by nucleoside
analogs are far subtler — so subtle that not all researchers
can agree on how, when, where or even if they are happening.
This chain of energy-producing steps takes place mostly within
tiny organelles carried inside nearly every cell in the body. These
cells-within-cells are called mitochondria, and they possess their
own set of DNA instructions to make some of the proteins they need
to perform the job of respiration. It's thought that nucleoside
analogs — some more than others — can, over time, affect
the quantity or quality of several of these crucial proteins by
interfering with the replication of mitochondrial DNA. The result
can be the generation of excess lactate and an energy deficit in
affected tissues; in nerve tissue, neuropathy can be a consequence.
Some scientists think a different form of mitochondrial toxicity
can trigger a cell to die directly through apoptosis. That could
be what's happening to fat cells. Obviously more and better research
is needed — fast.
Looking within the Limits
Researchers have been attempting to find a way to directly measure
mitochondrial toxicity by quantifying the amount of mitochondrial
DNA that can be recovered from cells. Some of this progress was
shown at the Lipodystrophy workshop. But serious objections have
been lodged against current versions of this technique because they
are liable to contamination from other sources of mitochondrial
DNA. Next year, the data from mitochondrial toxicity assays may
be more convincing, but for now, they're not ready for prime time.
One blood abnormality associated with ART, and with nucleoside
analogs in particular, is an increase in blood lactate levels. Slightly
elevated lactate levels are not noticeable, but as lactate levels
increase, symptoms such as nausea, abdominal pain and distension
may become apparent, causing tolerability problems. Lactate levels
over 5mmol/L in the presence of symptoms can indicate a rapidly
progressing, life-threatening illness called lactic acidosis. All
of the nucleoside analogs have been implicated in this rare lactic
acidosis syndrome and every person taking them should know the warning
signs: nausea, abdominal pain, fatigue or muscle weakness.
But the meaning of moderately elevated lactate levels, called hyperlactatemia,
is not certain, although many people believe nucleoside analog-associated
damage to mitochondrial DNA is a cause. Older studies of blood lactates
are difficult to interpret because of widely varying methods used
to collect and analyze the samples. Adoption of a strict new protocol
for the standardized collection and processing of blood lactate
samples will hopefully help dispel the fog that has surrounded the
meaning of these lab values.
One of the first tipoffs that metabolic abnormalities are afoot
is when blood lipid levels start to climb. The key movers are total
cholesterol and triglycerides. Rising cholesterol raises eyebrows
because of its association with cardiovascular disease — cholesterol
can clog the arteries feeding the heart and set off a heart attack.
But the underlying metabolic problems causing the cholesterol rise
and the role ART plays are still mysteries. The same is true of
the rise in triglyceride levels experienced by some people on ART.
Sustained high triglycerides may be a predictor for developing pancreatitis
or diabetes — and increasing rates of diabetes in people on
ART is a growing problem. How and why this is happening isn't certain.
Still, most clinicians would feel more comfortable if their patients
could achieve decent viral suppression without the abnormal labs.
A number of studies looking at lipid abnormalities have pointed
the finger at protease inhibitors and at ritonavir in particular
as causative factors. Recently a few more studies have shown that
nucleoside analogs add their own bump to cholesterol and triglycerides.
And a few high quality studies are starting to examine the associations
with actual fat loss and recovery.
Andrew Hill told the Lipodystrophy Workshop that there is a "Tower
of Babel" when it comes to reporting drug toxicities in clinical
trials, with at least seven different ways of reporting abnormal
lab values. Graded levels of toxicity are far less sensitive than
using continuous values such as changes in area-under-the-curve.
Drug company trials can either hide or accentuate toxicities depending
on the method chosen to report events. Often these studies just
add to the noise.
Leaping Lipids
Until recently, most of the research pointing the finger at Zerit
used methods that were easy to dismiss, such as small sample sizes,
no controls, and uneven reporting criteria. But this latest wave
of evidence is not so easily ignored.
A study presented in Barcelona (Gilead 903, sponsored by Gilead
Sciences, Inc., the makers of tenofovir) compared d4T with tenofovir
in 600 people over 48 weeks. All volunteers received efavirenz and
3TC. It was their first experience with HIV treatment. By the end
of the nearly year-long study, viral load reductions were about
the same in both groups. But there was a striking difference in
the cholesterol and triglyceride levels between those who took tenofovir
and those who took d4T. Triglycerides were unchanged from baseline
in the tenofovir group but went up by 74mg/dl in the d4T group.
Cholesterol also went up by 24mg/dl in the tenofovir group but increased
by twice that amount in the d4T group.
More data from Gilead 903 on the lipid profile of tenofovir versus
d4T was presented at ICAAC by Joel Gallant of Johns Hopkins University.
This trial is scheduled to run for three years — which counts
as long-term compared to most studies, but is little more than a
honeymoon in terms of how long most people will be taking these
drugs. So far — one year in — only lab toxicities have
been observed. Gallant made a point of stressing the need for longer-term
studies to help accumulate data that might finally correlate lab
values with clinical outcomes.
Earlier in the year, a Glaxo-funded study (ESS 40002) showed similar
findings at the Retrovirus Conference. As a part of this trial,
111 treatment-naïve patients received nelfinavir plus 3TC and
either AZT or d4T as the third drug in their regimens. With nelfinavir
in the mix, some increases in cholesterol and triglycerides would
be expected. But while people receiving AZT had cholesterol increases
averaging 32mg/dl, those on d4T had average increases of 45mg/dl.
For triglycerides, the results were even more striking with the
AZT group seeing a bump of 31mg/dl while the d4T group saw an average
increase of 69mg/dl — over twice as much.
Lactates in the Dock
In addition to looking at cholesterol and triglycerides, the Glaxo-funded
ESS 40002 study also recorded lactate levels at baseline and after
48 weeks. While people taking AZT experienced an average lactate
increase of 2.3mmol/L, those on d4T had increases over three times
higher, at 7.9mmol/L — well into the danger region.
Another Glaxo-funded study presented at ICAAC (TARHEEL) looked
at what happened when treatment-experienced patients who had been
on a regimen containing d4T and were experiencing lipodystrophy
switched to either AZT or abacavir. A subset of 16 people with elevated
lactates stopped all treatment until blood values showed a return
to safer levels. At that time treatment was restarted without d4T.
At 48 weeks lactate levels remained controlled within a normal range.
Although this small substudy lacks a control arm for comparison,
the results give guidance to a clinician seeking to normalize hyperlactatemia
in a patient.
The Proof is in the Padding
Laboratory abnormalities are intriguing for scientists and alarming
for clinicians but they are likely to be bewildering to people on
HIV treatment. It's often the changes in the way they look in the
mirror that matters foremost. Several studies are now starting to
connect the dots by evaluating changes in fat deposits under the
skin over time. For fat losses in the arms and legs, a technique
called DEXA is reliable and well accepted. For increases in fat
around the organs, a CT scan is a more acceptable — and more
expensive — method. For fat loss in the face, patient self-evaluation
or photography of facial fat wasting tell the story, but these,
unfortunately, do not carry the same weight as more objective readings
such as DEXA.
The report that's gotten everyone's attention comes from a large
trial that compared nelfinavir to efavirenz at the same time it
compared AZT/3TC with d4T/ddI in people starting their first ART
regimen. The trial, called ACTG 384, was conducted by the federally
funded AIDS Clinical Trials Group. Results were first presented
in July, 2002 in Barcelona and an additional analysis of fat loss
was presented at the Lipodystrophy Workshop.
The fat loss substudy of ACTG 384, (ACTG 5005s) measured subcutaneous
fat by DEXA in the arms and legs of 157 volunteers at baseline.
The results from comparisons at weeks 48, 64 and 80 were presented.
Overall, people in both the AZT/3TC group and the d4T/ddI group
experienced a brief increase in subcutaneous fat during the first
weeks after starting treatment. This may be due to a general improvement
in constitutional health that follows the initial suppression of
viral load. But by week 48, the average amount of subcutaneous fat
in the arms and legs had declined by 7.5 percent in those on d4T/ddI,
and was starting to drop, but still above baseline, in those on
AZT/3TC. By week 80, the d4T/ddI group was down about 15 percent
on average, while the AZT/3TC had slipped by about 7 percent.
When the same group was analyzed by whether they were on nelfinavir
or efavirenz, not surprisingly, a greater loss of limb fat was associated
with being on the protease inhibitor. At week 80, those on nelfinavir
plus nukes were down by 18 percent, while those on efavirenz had
sustained a 10 percent fat loss on average. A breakout of results
by individual three-drug combinations was not shown and the role
of d4T relative to ddI in causing fat wasting cannot be determined
from this data.
The TARHEEL study that looked at lactates also measured changes
in subcutaneous fat by DEXA after the switch was made from d4T.
Of the 118 people with lipodystrophy who enrolled, over 80 percent
had been on d4T for over two years. Three-quarters of the volunteers
switched to abacavir and the rest to AZT. At 48 weeks, the biggest
improvement was noted in the arms, with those on abacavir experiencing
an average 37 percent increase in subcutaneous fat and those on
AZT a 17 percent gain. Fat gains to the legs were less profound,
with abacavir associated with a 15 percent average increase and
AZT with about half that. However, a comparison of CT scans of visceral
fat at baseline and at 48 weeks did not show a significant change.
As with the lactate data, this is a before-and-after study with
no concurrent control, and other factors may have played a role
in these effects. Yet with the weight of evidence now implicating
d4T in accelerated subcutaneous fat loss, when is reasonable doubt
overruled by unreasonable risk?
Do You Feel Lucky?
It's likely that all of the nucleoside analogs contribute to mitochondrial
toxicity — some in some cells more than others; some sooner
than others. But d4T seems to offer a fast track to fat wasting
for far too many people who start taking it. Of course, not everyone
is affected — that's the quandary. Some people still have
fat and happy cheeks after years on d4T. If their viral load is
suppressed and they tolerate their drugs they'll probably see no
reason to switch. But people choosing a regimen today have a different
decision to face — and there's no way to predict how things
will go. If Zerit accelerates fat wasting, then there may be better
first choices for a nucleoside analog.
Many people on treatment and their doctors pronounced Zerit guilty
long ago. The next hearing should come when the committee that writes
the federal treatment guidelines meets again to redraw their recommendations.
My
New Liver by Larry Kramer
It is very, very hard to obtain an organ transplant in the United
States. First, there are so few organs available. Second, it is
hard to locate a transplant center willing to do coinfecteds —
that's what they call you when you have a virus like HIV with hep
B or C. Third, if and when they accept you, you have to wait in
line. Depending on which part of the country you are applying from,
and which medical center, it takes varying amounts of waiting time.
It never happens quickly. There is far too much red tape and bureaucracy
for that. Fourth, and perhaps first, you have to do an awful lot
of investigation, research, phoning, faxing, e-mailing, pestering,
even (how shall I put it?) raising your voice (politely, of course)
to accomplish any of this. Patient empowerment takes on new meaning.
You have to become a very fervent activist, for yourself. If you
aren't feeling so hot then you need someone with persistent and
unflagging energy to do it for you. You need such a person even
if you are feeling great. A transplant is something you simply cannot
enter into on your own. In fact, no transplant center will accept
you if you cannot show that your support system is visible and strong.
But if you know you are going to die if you don't get a new organ,
as was my case, you'd be surprised what a motivation this can be.
I was given six months and was down to the wire when I finally got
the call. At 67 I am the oldest person thus far transplanted with
a new liver. My surgeon says in all seriousness that you are as
old as your liver. I now have the liver of a 45- year-old man. Each
day I feel vital and vibrant. I have no side effects. My hepatitis
B appears to be gone from my body. And I truly feel like I am 45
again. Everything I went through was worth it, tremendously so.
You must investigate the half-dozen or so medical centers (the
number is growing) that will take us. You must never stop your efforts
to a) make a transplant surgeon evaluate you and b) get one to accept
you. Many people apply to several different centers, but that can
be very expensive. There are a lot of evaluation testing costs you
must bear before you can be officially accepted, and your insurance,
if you have any, picks these up only if and when you are accepted
for transplant. I was lucky. There happened to be a spurt of interest
in transplanting coinfecteds when I applied. It helps to be a scientific
curiosity. I believe I was the 22nd coinfected to be transplanted.
The NIH is currently preparing a research protocol to study transplants
for conifecteds; one of these days it will be approved and you might
qualify for that.
When you finally find someone willing to accept you, you have to
figure out how to pay for your transplant. No medical center will
take you unless you can prove up front that you can pay. Not long
ago if you were coinfected and looking for a new liver, you would
have been turned down by your insurance company because saving your
life was considered experimental. That's changed because of heroic
surgeons like John Fung at the University of Pittsburgh Medical
Center who knew better and proved it and confronted the insurers
himself. Still, insurance companies usually have to be challenged
if they turn you down, which on the first go-round they usually
always automatically do, hoping you will not appeal. Medicare rejected
me the first time but we appealed and in one day they had reversed
their decision. Empire Blue Cross, my secondary insurer, accepted
me immediately.
My liver transplant has cost Medicare, so far, over $500,000 and
Empire Blue Cross, so far, over $100,000 for the continuing medications
I must take, including a monthly pop of some $10,000 for something
called Hepatitis B Immune Globulin, which I believe I must receive
for the rest of my life. And you need to get your blood tested every
few weeks. That costs a lot too.
So we are not talking about an easy or inexpensive ride here. The
easiest part, believe it or not, was the transplant itself. I wasn't
in any pain, ever. The recuperation period is long; getting your
wind and motor abilities back can require many months of physical
rehab and taking it easy. You must have patience, which I don't.
Months of not doing anything can verge on the depressing. And if
you don't live near a transplant center, you may have to move close
by for the months of the whole process. My lover and care partner
(two different people, and I couldn't have got through the process
without either one of them) lived with me in Pittsburgh for many
months. I needed the love of my partner, David Webster, every single
minute. Boy did I need it. This is lonely and cosmically metaphysical
stuff to live through. (One day they tell you you're going to die,
and then suddenly you don't.) Hugs and kisses and smiles and homemade
food and constant gentle urgings that "you can do it"
sure help you get better faster. And I was not an easy patient.
I know that. And I needed the bossy efficiency of my very own Nurse
Ratchett, Rodger McFarlane, who had every secretary, nurse, technician,
and doctor at Presbyterian Hospital extra-attentive to his patient's
case.
I was additionally lucky because I was able to meet the criteria
for acceptance last year. I don't think I would have qualified under
new guidelines, called MELD (Model for End Stage Liver Disease),
which came into effect at the beginning of this year. The guidelines
were developed by the Mayo Clinic, and consciously or unconsciously,
MELD criteria appear to be blatantly discriminatory against coinfecteds.
As I understand them, and very little about the current or past
organ allocation system is understandable (even by the doctors who
get the organs), the abnormal blood markers they look for to be
considered for acceptance are not ones that people with HIV typically
have out of whack. For instance, my PTT, bilirubin, and creatinine
were not greatly elevated. But I was still dying and my liver was
still conking out. Yes, you say "go figure" a lot in this
whole process. And figure you do… or else you die.
Alas, most people in need of new organs don't make it. My memory
is filled with haunting images of desperately sick people in the
UPMC clinic waiting room hoping for a chance to grab an arriving
surgeon's arm and literally beg him or her for a liver. And of the
stories of uninsured recipients telling me how everyone in their
entire family or indeed community or indeed town had sold everything
they could to pay for their chance at life.
It shouldn't be like this, of course. We know all that. It is not
right to have a system that excludes most of the people who desperately
need its services. Yes, I know that I have been very, very
lucky. I can shout "Persistence!" to the world but all
activists have learned the hard way: we don't get anything without
a terrible fight. If we want to live, we must fight like hell. And
the fighting must never stop.
Larry Kramer co-founded Gay Men's Health Crisis and founded
ACT UP.
Botswana’s
High-Stakes Assault on AIDS By Roman Rollnick
Reprinted from Africa Recovery, United Nations Vol 16 No 2–3
www.africarecovery.org
The gleaming floors, white-frocked technicians and humming electronic
equipment of the Botswana-Harvard HIV Reference Laboratory here
in Gaborone, Botswana's capital, are distant in more ways than geography
from the dusty villages and crowded mining compounds on the frontline
of Botswana's desperate struggle against HIV/AIDS. But closing the
gap between the resources available at this modern new facility,
and the nearly 40 per cent of the adult population infected with
the deadly virus, is at the heart of Botswana's high-stakes effort
to provide comprehensive HIV/AIDS treatment to all of its citizens.
In January, Botswana became the first country in Africa to offer
expensive, but life-saving, antiretroviral drugs (ARVs) and other
medications to all who need them through the public health system.
It is a costly and ambitious undertaking, one that many health
care experts say cannot be done in Africa. But for the 330,000 Botswanan
adults estimated to be HIV-positive, access to ARVs and to ongoing
care, counseling and testing, is a matter of life or death. The
vast but sparsely-populated territory has the highest HIV infection
rate in the world. Some 26,000 people in this country of less than
1.6 million died from AIDS-related illnesses last year alone. "We
are threatened with extinction," President Festus Mogae told
the UN General Assembly last year. "People are dying in chillingly
high numbers. It is a crisis of the first magnitude."
More than Botswanan lives may be at stake, however. For years,
some international health experts, backed by many donor governments
and agencies and the powerful pharmaceutical industry, have argued
that poverty and the absence of infrastructure make it impossible
to successfully treat large numbers of HIV-positive people in developing
countries with AIDS medications. Rather than waste resources on
a failed effort to treat those already ill, they assert, scarce
funds should be spent preventing new infections through education
and prevention programs.
Activists counter that pilot projects have demonstrated the feasibility
of treatment programs in developing countries, and that only a combination
of treatment and prevention can turn the tide against the disease.
Many advocates charge that opposition to large-scale treatment programs
is fueled more by concerns for patent rights and profits than genuine
doubts about practicability.
Botswana is the first African test case. Success in treating large
numbers of patients will buttress the argument for greatly expanded
treatment efforts in the rest of Africa and other developing regions.
Failure will badly undermine the call for greater treatment access
for the world's poor. Although the Joint UN Program on HIV/AIDS
(UNAIDS) has long maintained that both prevention and treatment
are necessary in the campaign against AIDS, fewer than 30,000 of
the almost 29 million Africans infected with the virus have access
to the ARV drugs that have dramatically reduced death rates in rich
countries.
Slow but Steady Progress
If any country in sub-Saharan Africa can implement a comprehensive
HIV/AIDS prevention care and treatment program, observers say, it
is Botswana. Unlike many of its neighbors, the country has enjoyed
an unbroken period of peace and comparative prosperity since independence
in 1966. Its government is widely regarded as among the most efficient
and capable on the continent, and its annual per capita income of
$3,300 is among the highest.
Still, the obstacles are formidable. Many Botswanans are migrant
workers, employed in neighboring South Africa for much of the year,
but maintaining farms and families back home. Migrants are at particular
risk of infection because of the increased likelihood of contact
with prostitutes and other casual sex partners while away from home.
Often unaware that they have become HIV-positive, and unwilling
to seek out testing and counseling because of the stigma associated
with the disease, migrants are thought to be an important factor
in the spread of the virus.
For those who do seek medical help, there is the problem of locating
it. For HIV patients outside the private sector, there are only
two government referral hospitals, one in Gaborone and another in
the north, in Francistown. There are two smaller district hospitals
in the country, but most public health care is delivered through
local clinics offering only basic services.
The National AIDS Coordinating Agency (NACA) formally embarked
on the national treatment program in January of 2002. Dr. Banu Khan,
NACA's national AIDS coordinator, explained that the government
set a target of 19,000 people for enrollment in their first year
of ARV treatment under a $27.5M program in which people who require
the drugs will get them for life. The ministry of health has calculated
the cost of medications, testing and counseling at about $600 per
person, per year. Over the first five years of the program, the
Gates Foundation will provide $50M to help Botswana strengthen its
primary health care system, while the giant U.S. drug manufacturer
Merck will match that contribution with anti-retroviral medicines.
The other half of the cost, some $100M, will be met by the government.
"As of June this year, we had an estimated 1,000 people enrolled,"
Dr. Khan noted. "We have 500 undergoing the treatment, while
the remainder are still being screened to ascertain their precise
treatment requirements." She termed that number "disappointingly"
low, but said that more people are steadily coming forward. NACA
says the volunteer patients include a "good mix" of educated
and poorer rural people, some from the remote regions of the arid
Kalahari in the west and northwest of the country.
Significantly, NACA officials say, initial indications are that
very few patients have difficulty adhering to the complex ARV drug
treatment regimes. The ability of poor and poorly educated patients
to stick to strict medication schedules over a lifetime has been
a major concern of health specialists and is an important aspect
of Botswana's treatment initiative. Like Alcoholics Anonymous, NACA
operates a "buddy system" whereby each patient is encouraged
to form a special bond with someone close, who makes sure they remain
on their medication schedule. The patients, in turn, counsel others
who feel they may need help to come forward.
Enrolling Mothers
Enrolling women in the program is a key priority because they make
up more than half of all infected adults. Dr. Khan said that NACA
is especially concerned at the low intake of mothers in a program
intended to cut mother-to-child transmission of the HIV virus and
keep infected mothers alive. Since the pilot project began, she
said, only 2,000 women are currently undergoing treatment for AIDS-related
illnesses. "We only opened up pilot sites two years ago. The
percentage of mothers enrolled, however, is not desirable. It is
low and must be increased. We have problems here, especially the
one of stigma." Health officials said enrollment by pregnant
mothers had only been in the 11–20 percent range.
"Another problem is the status of women in relation to men,"
Dr. Khan added. Many women lack the power to control decisions about
sexuality and remain under the authority of husbands, parents and
in-laws all their lives. "How do you test someone if they do
not get permission?" Dr. Khan asked.
"Then, with those who do enroll, they go home to a remote
village with formula milk for their baby and are branded as suspect
because they are not breast-feeding.... Mothers also worry about
who will look after their baby if they die. But ARV therapy is now
available in Botswana for these mothers and their babies, and I
am hoping [enrollment] will increase now."
The country currently has 16 voluntary counseling and testing centers
specifically for mothers — one in every district. These are
stand-alone centers where one can discuss medical problems in privacy.
"In the latter part of last year, we had a conference for people
living with HIV/AIDS and it drew 500 people," Dr. Khan noted.
"They went back to their homes and formed support groups to
reduce stigma."
Dr. Khan said that NACA urgently needs more trained staff. "We
have found that if you have a trained nurse dealing with many people
in a rural clinic, for example, she does not have the time to counsel
every HIV patient. So we are building a system of lay counselors,
like social workers. For this, we do not necessarily need nurses
and we have a program to employ 500 such lay counselors. We are
hoping they will also play a key role in reducing stigma."
She said that people living with AIDS, both from the educated urban
classes and rural communities, are increasingly aware that the government
is providing free lifelong treatment. "These people are with
us on a voluntary basis. No one is coerced. We counsel them on positive
living, about prevention, about the importance of remaining on the
treatment even if they feel better. And they usually go home and
spread this positive message."
Staff Shortages Severe
At present, NACA employs 10 doctors working full time on HIV/AIDS
at the Princess Marina Hospital in Gaborone, and five at each of
the other hospitals. Patients are also seen at the smaller health
facilities, some of them mobile clinics, around the country. Uniquely
for an African country, NACA says, almost no one is more than 8
km away from a clinic where they can seek medical help. Even in
the remotest areas of the Kalahari, most people are just 15 km away.
These clinics decide what sort of treatment people need, and either
refer them to a hospital or provide them with ambulance transport
if required.
Ms. Catherine Sozi, a British-trained Ugandan doctor based at the
UNAIDS office in Pretoria, South Africa, said Botswana can sustain
its national health scheme for AIDS patients even though the drugs
are required for life. "However, there is an acute, absolute
shortage of doctors, nurses and counselors in Botswana's health
care system," she said, citing a recent UNAIDS assessment.
"Although we did not have time to calculate the number of extra
health workers needed for the ARV program, the numbers are substantial.
If a first recruitment for ARV treatment would cost one hour of
a doctor's time, recruiting 10,000 new patients in three months,
for example, would require at least 20 full-time doctors doing nothing
else but supervising these patients."
The shortage of doctors, pharmacists, nurses and counselors is
compounded by the fact that over 90 percent of doctors in Botswana
are foreigners who do not speak Setswana. Counselors too are recruited
from abroad and need to spend time becoming familiar with the local
culture. Many spend only a brief period in the country, thus exacerbating
the need for frequent training and supervision to ensure proper
medical care. There also is concern that many nurses, once trained
and registered, emigrate to better-paid jobs abroad.
The government is seeking to recruit up to 200 new doctors from
South Africa, Cuba and other nations to administer the drug program.
"In return for their travel and accommodation expenses, many
are coming to give their time free of charge," Dr. Khan explained.
"They know the government is serious in addressing this epidemic."
The shortage of pharmacists outside the major hospitals is another
problem. UNAIDS found that Botswana's few pharmacy technicians already
have to manage drug supplies and distribution in the hospital and
surrounding clinics. "They need support if they are to handle
sensitive drugs like ARVs," Dr. Sozi said. Because Botswana
will have to rely for some years to come on foreign health professionals,
she noted, UNAIDS is recommending appropriate courses for them about
local culture, health policies and protocols. Many current staff
will require crash courses on ARV treatment issues.
Testing, monitoring and surveillance of the Botswana AIDS plague,
as many now call it, is carried out by the new Botswana-Harvard
laboratory at the Princess Marina Hospital. The first of its kind
anywhere in Africa, the laboratory, with a staff of 50, is equipped
with gene sequencers and blood cell sorters, enabling scientists
to keep track of the spread of HIV, especially the HIV-1C strain
prevalent in this part of Africa.
Combining Treatment and Prevention
Botswana is supporting the new drug treatment policy with an expanded
and more aggressive education campaign, modeled in part after Uganda,
which has successfully reduced new HIV infections through sustained
public education. President Mogae is determined to make sure that
the message of free treatment gets out — through radio, billboard
campaigns and by word of mouth.
Mr. Edmund Dladla, national coordinator of the Botswana Network
of People Living With HIV/AIDS, welcomed the president's leadership.
"Any person who is of working age, who has a job and some education
talks about it. And everyone wonders about the impact AIDS is having,
not only on those close to them, but also on the country as a whole.
People are scared."
"For a decade," he continued, "until the end of
the 1990s, we were in a state of denial, blaming the crisis on foreigners.
Then, as we realized its extent, we started acting. Today, I would
say the government is very transparent, pro-active and accountable.
We are the most advanced African nation in this struggle —
and believe me, I would not have said that just three years ago."
Employers Get Involved
Botswana's private sector has also become involved. Three years
ago, the country's biggest employer, the Debswana diamond mining
company, realized after testing its 6,000-strong workforce that
fully a third of workers aged between 24 and 40 were HIV-positive.
With revenues of some $1.8B dollars a year, and skilled miners scarce,
the company set up its own HIV/AIDS scheme.
"We realized we had to do something fast because diamonds
are the foundation of our economy," said Ms. Tsetsele Fantan,
director of the company's program. She said Debswana agreed to provide
free treatment for each infected employee and one legal spouse,
while the government would provide treatment for other partners
and their children. The government has also urged major banks, transport
companies and even petrol stations to provide better levels of health
care and make HIV counseling and treatment available to their employees.
"This collaborative program is designed to demonstrate the
benefits of a comprehensive, multi-sectoral approach to improving
the care of people living with HIV in a country with limited resources,"
said Dr. Clement Chela, of the Botswana Comprehensive HIV/AIDS Partnership.
The fact that ARVs are now freely available, he added, has become
a motivating factor for people to come forward. "The program
we have put in place here can work in other countries in Africa,
and with international financial help, it can be sustained."
Drug
Fact Sheet Review At the Barcelona AIDS Conference,
an international network of treatment advocates met to begin laying
groundwork for a treatment preparedness project for resource-poor
settings. The goal of treatment preparedness is to increase awareness
of the promise and realities of antiretroviral therapy in anticipation
of their availability and to educate and mobilize well-informed
local advocates. A preliminary stage of this project has begun to
collect and evaluate existing educational materials that can be
used as written, or as a model for locally produced materials. Several
sources of drug fact sheets and treatment information resources
are reviewed here.
Methods: An Internet search was made during the week of
September 16, 2002, to identify HIV drug fact sheets and other HIV
drug information resources. Information about the nucleoside analog
3TC (Epivir, lamivudine) was selected and copied into a text document.
This material was evaluated for its discussion of the drug's action
and of its side effects. The texts were graded on the criteria of
accuracy, currency and clarity. The reading level of each resource's
entire 3TC entry was assessed using the Flesch-Kincaid Reading Level
utility internal to Microsoft Word. After the specific sections
were evaluated, each criterion was graded and an overall score was
assigned. Finally, a brief assessment of the source's additional
resources was noted.
Results: Treatment information resources available on
the Internet can be divided into two categories based on the mode
used to address the reader, on the format used to discuss serious
side effects and upon the Flesch-Kincaid reading level.
Simple Fact Sheets: Simple language fact sheets tend to
address the reader directly, i.e., "You should know…"
Simple fact sheets also tend to list the most common side effects
before warning about rare potential adverse events. The reading
level of simple fact sheets ranged from 7.4 to 10.0. These fact
sheets are designed to be used by clients who may be learning about
HIV treatment for the first time.
Treatment Information Resources: Treatment information
resources tend to discuss information objectively and reference
clinical trial evidence. Serious side effects are usually listed
first as is typical of information presented to health care professionals.
Reading levels are at the top end of the scale (11.0–12.0)
These resources can be used by educated or motivated readers, or
as a "wholesale" source of information that is ultimately
retailed to clients through treatment educators.
Simple Fact Sheets
+ + +
Treatment Information in Asian Languages
Asian Community AIDS Services (ACAS)
Ontario HIV Treatment Network
www.acas.org
Last updated: July 2001
Languages: Vietnamese, Chinese, Tagalog, English;
Formats: PDF, English text available online
Reading Level: 7.6 |
ACAS offers a charming fact sheet, if that is possible. The lightness
of language and clarity of ideas is refreshing. The notion that
HIV drugs can "help you get your health back" is touching
and true — a message not seen elsewhere. The clear descriptions
of the types of blood cell deficiencies may not be necessary, but
they are edifying. There are a few awkward grammatical passages
in the English version that could have been smoothed by a proofreader.
I'm told the Chinese translation is formal but clear on the facts.
The tone of this material is non-judgmental and unfailingly polite:
"3TC does not kill the virus or cure AIDS. It also does not
prevent the transmission of HIV, so please remember to always take
precautions if you are having sex (e.g., use latex condoms) or using
drugs (e.g., use clean syringes)."
The producers of these fact sheets seem comfortable with a harm
minimization approach to treatment education, advising, for example,
not to skip a dose just because you want to have a drink. But this
fact sheet takes harm reduction a little further: "3TC liquid
contains sugar, you should clean your teeth regularly after taking
the medication to prevent tooth decay."
Treatment Information in Asian Languages is available as text or
in a PDF format as a two-page handout. The design is simple and
does not rely on graphics or color. This fact sheet is rivaled by
New Mexico AIDS INFOnet for its simple reading-level score but runs
about a third longer and packs in more concepts with grace. Top
honors.
+ + 1/2
New Mexico AIDS InfoNET
www.aidsinfonet.org
Last updated: July 14, 2002
Languages: English, Spanish
Formats: PDF, Word, Text
Reading Level: 7.4 |
New Mexico AIDS InfoNET's fact sheets are very popular with educators
for their simple language and consistent format. But one of the
casualties of simple language is loss of precision and accuracy.
There are occasional lapses into unexplained concepts here, such
as genetic code, or the use of medical terms like hypertension instead
of high blood pressure.
One problem with the freshness of InfoNET fact sheets is that they
are widely distributed by third parties that may not have the latest
version on line. For example, the 3TC fact sheet found on AIDS.org
is dated February 7, 2002, and lacks news of the approval of once-a-day
dosing found on the main InfoNET site.
The fact sheets are organized by category and reference related
fact sheets by number. However, the web site itself is cluttered
and it can sometimes be difficult to locate what you want. All of
AIDS InfoNET's many fact sheets are translated into Spanish and
can be downloaded in a format ready for the Xerox machine.
+ +
Positive Words
www.positivewords.com
Last Updated: 2001
Languages: English, Spanish
Formats: PDF, Simple Text, Online Text
Reading level: 9.5 |
This fact sheet manages to educate about broader concepts while
informing about 3TC in particular. Readers are advised to tell their
doctors about any street drugs used. They are also advised to space
their dosing when taking 3TC with ddI. The "why" is given
along with "dos" and "don'ts". This is a commercially
sponsored site, however editorial independence is protected by a
panel of community advisors.
Positive Words offers an abundance of brief, easy to read articles
about a wide array of HIV-related topics. If you can manage to navigate
the confusing site, you can find some basic drug fact sheets that
balance readability with accuracy and brevity.
+
JAG Enterprises
www.jag.on.ca/pdf/Antiretrovirals
Last Updated: October 2000
Languages: English, French, Spanish
Formats: PDF
Reading level: 10.0 |
JAG Enterprises in Ontario, Canada, produces a series of HIV informational
pamphlets for patients. These pamphlets have a friendly yet professional
tone with enough white space to minimize the intimidation factor.
Yet there is a pervasive tone of authority that many users may find
disrespectful. For example, women are simply told they must use
birth control methods with no discussion of why.
The reading level is fairly high and terms such as inhibit, abdominal
and gastrointestinal are not defined within the text. Certain medical
terms, such as neutropenia and pancreatitis are explained. The materials
were written by a pharmacist (which may explain the tone of authority)
and the site is sponsored by several major pharmaceutical makers.
The colorful, illustrated fact sheets are preformatted and ready
to print. The drugs are pictured in color photographs and there
are spaces provided to note a persons's dosage and contact phone
numbers.
+
AIDSmeds.com
www.aidsmeds.com
Last updated: June 24, 2002
Languages: English
Formats: Online text
Reading level: 9.5 |
AIDSmeds.com is intended to be a patient-friendly place for people
considering or already taking antiretroviral therapy. And for the
most part the writing is accessible. But after reading the long
list of cautions and warnings here, it would be a wonder if anyone
actually had the nerve to get a prescription filled. This is the
place to go if you need to find out how to deal with a 3TC overdose
(seek emergency medical attention). There is a clear presumption
that the reader has unlimited access to medical advice; readers
are advised to consult their doctors no less than twenty times on
one page. Mixed in with all the cautions is the odd suggestion that,
"Lamivudine may also be used for purposes other than those
listed in this medication guide." Cake decorations?
It was interesting to compare the 3TC entry to that for a more
recently approved drug, tenofovir. The writing style and format
is completely different and the obsessive warnings are mostly absent.
For the newer drug, efficacy is discussed and the evidence is referenced.
Despite some spelling errors, it delivers a far more useful plate
of information. This is a commercial site and affects an active
magazine-like design that is visually busy and sometimes overwhelming.
AIDSmeds.com is a great resource for someone with time to browse
everything that is offered and has a 24-hour hotline to a physician.
AIDS Treatment Data Network (ATDN)
www.atdn.org
Last updated: August 22, 2002
Languages: English, Spanish
Formats: Online text
Reading level: 11.5 |
Older fact sheets often retain artifacts of when they were first
written — when combination antiretroviral therapy was still
new: "Many studies have now shown that using lamivudine in
combination with at least two other anti-HIV drugs can prevent the
virus from getting resistant." The benefits of combination
therapy may now be considered dogma; it's better to simply stress
the importance of using at least three meds together on a consistent
basis; no combination in itself can prevent resistance. The dated
tone and inaccuracies aside, grammatical errors, spelling errors
and typographical errors will erode a reader's confidence in this
material. It's time for a rewrite.
HIV Nordic Net
www.nordicnet.org
Last updated: 2000
Languages: Danish, English, Finnish,
Icelandic, Norwegian, Swedish
Formats: Online text
Reading level: 12.0 |
This material seems to have been translated into English and suffers
from frequent awkward Nordic sentence structure: "…a
real need to be aware of what they are is important for you to know."
There seems to be a tautology in saying the drug "is normally
very well tolerated by most patients who experience little or no
side effects." It's the ones with lots of side effects that
have trouble with tolerability. This material is rated at a high
literacy level — for no reason other than the awkwardness
of the writing.
GMHC Fact Sheet
Gay Men's Health Crisis
www.gmhc.org
Last updated: May 2000
Languages: English, Spanish
Formats: Online text, paper copies
Reading level: 10.3 |
GMHC does not currently offer a fact sheet for 3TC. For the purposes
of this review, a fact sheet for Viramune was substituted.
These fact sheets are written in a conversational style, but that
does not mean they are simple to read and understand. The discussion
of side effects is poorly organized, with the risk of rash mentioned
first, followed by common, mild effects, then back to liver side
effects, which can also be life threatening — a fact not made
clear here. The statement, "Viramune...has been known to cause
hepatitis..." could easily cause confusion: does Viramune cause
hepatitis C? For a drug with potentially far more serious toxicities
than 3TC, this lack of clarity is unacceptable. GMHC says a new
series of fact sheets is due out soon.
Project Inform
www.projectinform.org
Last updated: July 1997
Formats: PDF, Online text
Languages: English, Spanish
Reading level: 11.7 |
The material on this site is so old it would be laughable if not
for the potential to mislead innocent readers: "... a number
of ongoing studies are evaluating triple drug combinations which
utilize AZT, 3TC and protease inhibitors (notably indinavir, also
known as Crixivan)." Other reports of "ongoing" studies
about double nucleosides are alarming. Warnings about lactic acidosis
are absent. Accurate for the time when they were written, but not
now, these fact sheets belong in a time capsule. They should be
taken down until they are rewritten.
Treatment Information Resources
+ + +
AIDSmap
www.aidsmap.com
Last updated: July 29, 2002
Languages: English
Formats: Online text
Reading level: 11.0 |
AIDSmap is a bright light in this constellation of treatment information.
It begins with one of the better simple-language explanations of
what 3TC does. In addition to listing the usual side effects, AIDSmap
gives some advice for how they can be minimized, when they will
be worst, and who might have more trouble than others. All efficacy
statements are evidence-based and referenced. The site is up-to-the-minute
and was the only one reviewed to include a report on the ACTG 384
study presented at the Barcelona International Conference in July.
Medical jargon is usually explained in parenthesis, although occasionally
terms such as "resistance" are introduced without definition.
Overall, the reading level is higher than one would like for a simple
fact sheet and the voice sometimes swings between direct address
and third-person.
AIDSmap is unique in that it is scalable: the overview can expand
into a review of virtually every clinical trial result ever published.
Users of this site can go as deep as they like into what is known
about 3TC. The site is also optimized for international treatment
preparedness workers with the trade names of Indian generic versions
of 3TC (Lamivir) listed along with Glaxo's. Best of the bunch.
+ +
amfAR Global Link
www.amfar.org
Last updated: June 2002
Languages: English
Formats: Online text
Reading level: 12.0 |
This material is not intended for "retail" treatment
education but gives a capsule review of all the salient points that
a medical professional would want to know about 3TC. Safety issues
are highlighted and key references are provided. Although the material
has been recently updated and includes results of a tiny study of
once-daily dosing, the important results from ACTG 384, presented
in Barcelona in July, have not yet been added. Global Link should
be useful to creators of treatment education materials as a source
of reliable facts. Anyone who'd like to improve their knowledge
of HIV treatment, complications and infections can find a wealth
of information at Global Link. Hours of good browsing here.
+ +
AIDS Clinical Trial Information Service
(ACTIS)
U.S. Dept. of Health and Human Services
http://www.actis.org
1-800-TRIALS-A
Last updated: July 17, 2002
Languages: English, Spanish
Formats: Online text, telephone
Reading Levels:
Technical View: 12.0
Non-technical View : 11.5 |
Technical View
Fact sheets for PhDs. A scholarly review of what is known about
3TC right down to the drug's molecular weight and melting point
(160°–162° C). Absorb this information and write your
own fact sheet.
Non-Technical View
ACTIS (thankfully) boils down all the information contained in the
Technical View into a simple one-page summary.
Although this is the non-technical version, the 3TC summary is
written at a relatively high reading level, with many clauses and
semicolons lengthening the sentences. Side effects are clearly described
without jargon, and the less serious effects are put in context
of when they are likely to occur. The term enzyme is defined but
not necessarily in a way that will be meaningful for understanding
its role HIV replication. The discussion of side effects makes the
useful point that drugs have effects on the body — some desirable,
some not. It may be that the cost of maintaining accuracy and clarity
is the loss of simplicity. Overall, a great source of reliable information.
Short Course Notes on HIV drugs
in development
Pro-Drug Lobby
Glaxo presented data on their "908" drug (formerly
VX175) a version of Agenerase with a better pill burden and
much improved tolerability. The trial compared 908 to nelfinavir,
both in a twice-a-day regimen with abacavir and 3TC. At 24
weeks, drops in RNA and gains in CD4 counts were similar.
If starting with viral load under 100,000, there was a similar
likelihood of achieving VL under 400 copies. Glaxo's drug
showed it's modest potency edge in those who started with
VL above 100,000 at baseline. Your mileage may vary.
As expected, there was three times as much diarrhea on the
nelfinavir arm. Triglycerides were lower on 908, an advantage
that will likely go out the window if Glaxo shoots for once-a-day
boosting with ritonavir. One note: the incidence of abacavir-associated
drug allergy in this study ran between 5 and 8 percent, similar
to the rate in the TARHEEL study — both higher than
the 3 percent rate that Glaxo often quotes. Two other Phase
III trials of once-a-day 908 plus ritonavir are underway.
Data could go to the FDA next year.
Fresh Air
In his presentation of tenofovir data during a late breaker
session at ICAAC, Joel Gallant of Johns Hopkins University
prefaced his talk with a verbal disclosure of his relationships
with various pharmaceutical companies. This was a first in
my experience; it seemed to cause Dr. Gallant no pain, no
one walked out, and the ceiling of the conference center did
not collapse. His public disclosure put his cards on the table
and allowed the data to be evaluated in the open air. Gallant's
breakthrough should become the model for all presenters of
clinical trial data.
Onward T-20
The FDA announced they have given T-20 priority review status
for approval, which means they must say yea-or-nay by March
16, 2003 — although the agency could act sooner. T-20
sponsor Roche is happy about this, but a persisting problem
with drug production has them downplaying expectations about
actually being able to deliver the drug to everyone who'll
need it. Roche has scheduled a meeting with community members
next month to discuss this issue, its expanded access program,
and rumors of "golf-ball-sized nodules" at the site
of injection. Physicians are returning from Roche training
sessions buzzing about the importance of learning proper T-20
preparation and injection techniques. Not a bad idea.
Atazanavir Update
At ICAAC, Kathleen Squires presented 48-week data on Bristol
Myers Squibb's low-tox PI hopeful, atazanavir (ATV). BMS 038
compared ATV head-to-head with efavirenz, both once a day,
each backed up with standard BID Combivir. Both drugs turned
in respectable efficacy results, each bringing similar proportions
of the 810 treatment naïve participants below 400 copies,
although only about half as many went below 50 copies. Resistance
to ATV was uncommon, and a tantalizing suggestion was floated
that ATV resistance, when it does occur, may possibly increase
susceptibility to other PIs.
The great promise of atazanavir is that lipid abnormalities,
which have been the bane of other PIs, seem to be absent with
this drug. Triglycerides were somewhat elevated in the efavirenz
group but actually went down for those on ATV. But this PI
has one peculiar trait that will bear watching — elevated
levels of unconjugated bilirubin are associated with ATV and
produced 21 cases of jaundice in this trial. If this turns
out to be a significant problem with TAZ, unkind consumers
could take to calling it The Yellow Peril.
This large, worldwide study enrolled people into one of the
broadest cross-sections of the world epidemic yet studied
in a drug company trial and the demographics are notable.
Over one third of the participants were women and about two-thirds
were non-white. Hopefully, this kind of representation will
reflect a trend in Phase III clinical trials to come.
|
Global
Treatment Update
By Bob Huff
Global Fund Slow to Take Off
The Global Fund for TB, Malaria and HIV has said that despite approving
a first-round of initiatives in the spring worth $1.6B, no money
has yet been disbursed. A second wave of funding requests, currently
being evaluated, and subsequent waves, may push commitments to over
$8B within the next two years (UN Secretary Kofi Annan estimates
the need is $10B a year). Yet it's not clear at this point if the
Fund will even have the cash to meet its initial check run. As of
September, the Fund had only $500M in the bank to give out. Despite
having received pledges of over $2B from world governments, there
is a large gap between what has been promised and what has been
deposited in the Fund's account. Furthermore, money that is available
to be disbursed has been held up as the Fund establishes procedures
to route the money and provide accountability. News reports have
said the Fund is still struggling to get on its feet operationally
and even lacks working voice mail on its telephone system. Still,
requests for funding continue to stream in.
On a positive note, the Fund has finally given guidance to grantees
over the issue of generic medications. Bucking intense pressure
from the pharma lobby, grantees now have a green light to seek drugs
at "the lowest price possible," whether generic or branded.
Excerpt from a speech by Stephen Lewis
The Center for Strategic and International Studies —Washington,
D.C., October 4, 2002
I'm no optimist about the virus. But I simply don't believe, on
the basis of personal observation, that we have to face Armageddon.
In fact it enrages me the way in which we pile despair upon catastrophe,
over and over again, rendering everyone paralyzed. You don't have
to be some pathetic bleeding heart to see the potential strength
in these societies at the grass roots, and know that if we could
galvanize the governments, indigenous and external, and equip civil
society, and address capacity and infrastructure with external resources,
then we could defeat this pandemic. It is not beyond our competence.
I met not long ago with a thousand high school students in Addis
Ababa, for a question and answer session that lasted an entire afternoon,
and the intelligence and understanding and sophistication of those
kids gives nothing but hope; I've met with the WFP truck drivers
in Nazareth, south of Addis, as they tell their stories of the training
they receive, and how they now always carry condoms on their routes;
I've met at length with his Holiness, the Patriarch of the Ethiopian
Orthodox church as we discussed how the UN family could set in process
training for his 350 thousand priests so that they, in turn, could
address their parishioners; I've sat over coffee with village women
miles and miles from the Ethiopian capital, while neighbors gather
to talk about how the virus is transmitted and how to protect themselves.
They laugh self-consciously in the presence of a stranger, but they
don't mince words.
I've attended the two day sensitivity sessions in Abuja, Nigeria,
for the establishment of mother-to-child-transmission clinics —
a tremendously impressive undertaking; I've sat with the doctors
and nurses in a leading hospital in Benue state as they decide how
they'll choose those who should receive anti-retroviral treatment
when it begins, and how to handle the counseling; I've met with
groups of People Living with Aids out in the Eastern region, near
Onitsha, as the mothers talk about the kids they'll leave behind,
and then make their eloquent, moving, unanswerable plea for treatment.
Coke Announces Plan — Pressure to Continue
AIDS activists have been demanding that international Coca-Cola
and it's local independent bottlers in Africa agree to pay for HIV
treatment for all who need it among the 100,000 people employed
to bottle and distribute Coke. On September 29, 2002, Coke, along
with eight of the 40 bottlers they work with in Africa announced
a plan to share the costs of AIDS treatment. According to a Coke
statement: "The first bottlers to deploy the program are in
Egypt, Morocco, Burundi, Congo, Democratic Republic of Congo, Reunion,
Angola, Rwanda, Kenya, Tanzania, Ethiopia, Mozambique, Namibia,
South Africa (some), Uganda, Botswana, Lesotho, Swaziland and Zambia.
Given some of the infrastructure challenges, it will take up to
12 months to fully roll this out in these countries." The cost
to Coke is estimated at about $5M per year.
Yet activists say this plan falls short on a number of counts.
First, unless Coke presses holdout independent bottlers to join
the plan, only a portion of Coke's workers will be covered. Second,
the current plan will exclude children of Coke's workers. Finally,
the plan intends to require a 10 percent co-payment to receive drugs.
Activists fear that this amount — easily affordable by the
company — may pose an insurmountable barrier for many low-pay
workers.
We Must Have
Presumed Consent By Larry Kramer
More and more people with HIV and/or hepatitis B and/or hepatitis
C are going to need organ transplants, particularly liver transplants.
This is not an opinion. This is a fact. As more and more of us all
over the world discover we are carrying one or more of these viruses,
even if we are being treated for them — or particularly if
we are being treated for them — the more likely it becomes
that one of our organs is going to cease working effectively. And
the longer we are being treated, i.e., the longer we live, the more
that chance grows.
With all the new drugs for HIV and viral hepatitis, it is now safe
— ok, kosher to transplant "coinfecteds," which
is what people with viruses are called in the transplant world.
The New England Journal of Medicine has even written approvingly
of such procedures. Insurance companies can no longer simply refuse
to pay for these hugely expensive procedures on the grounds that
they are "experimental." These operations are no longer
experimental. Too many of them have been done successfully.
Right now there are hundreds of thousands of people in this country
waiting for organs. Most of them will die before they get them.
Many of them will die after they have been put on a waiting list.
Why is this?
Because not enough people in America donate their organs to be
used after they die.
It is as simple and as complicated at that. There are more than
five people waiting for every organ made available by donation.
In many foreign countries this extreme shortage does not exist.
That is because these countries (and they include Austria, Belgium,
Denmark, Finland, France, Italy, Norway, Singapore, and Spain) have
what is called a Presumed Consent organ collection system. That
means that every person in that country is deemed to be an organ
donor unless s/he specifically opts out. That means that when an
accident occurs to a person who has not opted out, and brain death
is declared, his or her organs can be taken immediately without
the time-wasting rigmarole America requires for "approval."
An organ only has a few hours to get from one body to the new one.
In America you sign the back of your driver's license if you are
willing to be a donor, and even then most centers still require
permission from a family member, which, believe it or not, may not
be given.
I have been trying, since my transplant, to find a way of changing
America's organ donor system to one of Presumed Consent. Well, you
would have thought that Presumed Consent was akin to the biggest
blasphemy known to civilization. Opponents from the right, the conservatives,
the orthodox, you name it, including, believe it or not, the ACLU
(did you know that the dead had rights?) have screamed in opposition.
These opponents do not care that Spain, a very Catholic country,
has the best organ procurement system in the world.
And no one I can find knows how the system can be legally changed.
Who does it? Congress, by passing a law? HHS, by issuing an edict?
State by state or community by community, by putting it on a local
ballot? As Robert Bazell, the chief medical correspondent for NBC
Nightly News, warned me when I embarked upon this new activist journey,
"Larry, you will find that it is like punching air."
The one person who can help change this system more than anyone
else is Senator Bill Frist (R-TN). He is a transplant surgeon himself.
He knows the hideous horrors of watching people desperate for organs
die. But he is a politician, and a Republican, and from the South,
so he is not exactly willing to be Mr. Flag Waver for organ transplants.
He has prepared a bill, with Sen. Christopher Dodd (D-CT), to investigate
Presumed Consent. But this bill has no hope in hell of getting passed,
which is not so bad because it is such a wishy-washy, namby-pamby
piece of stand-in-place legislation that we are better off without
it.
AIDS activists have been here before. It is the beginning of a
new crisis and no one of any importance wants to pay it an iota
of attention. In the coming years the number of people around the
world waiting for new organs is going to rise to the millions from
the several hundred thousand currently in need. Once again I find
myself screaming out loud about a huge and coming catastrophe and
find that no one is listening.
I would like to close with some words from Dr. John Fung, who saved
my life: "Patients are dying and the public still does not
understand that saying no to donation means someone will die. No
one wants to be so blunt — no one wants to raise the American
conscience to make people feel that it is their human obligation
to pass along their body to the living when they die. This is a
systematic deficiency in American culture, the idea that you are
out only for yourself and have little or no obligation to society
as a whole."
Tell Senator Bill Frist: America must have presumed consent!
Bill_Frist@frist.senate.gov
or call: 202/224-3344
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