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Past Issues
Volume 16, number 9
September 2002
Contents
ADAP Cuts Feared
Tell Congress to bridge the gap in funding
Sexual Transmission of HCV?
People with HIV may have a higher risk
Reading Virology
Protein interactions take center stage
I was a Twenty-Something Outreach
Worker
A provider learns to provide for herself
Short Course
Notes on drugs in development
Global Treatment Update
Big mining jumps on board.
Coke drags its heels
Opinion
Gregg Gonsalves targets government obstruction of rapid tests
ADAP
Emergency!
By the Save ADAP Committee
AIDS Treatment Activists Coaliton (ATAC)
The AIDS Drug Assistance Program (ADAP) is a federally funded program
intended to provide access to HIV/AIDS treatments for low-income
people who are uninsured or lack adequate prescription drug coverage.
The program is administered by the states and, in some cases, additional
state funding augments basic drug coverage. Because the extent of
coverage offered is left to the states to determine, various programs
may differ considerably in the number of drugs on the formulary,
ancillary services covered, and in financial and clinical eligibility
criteria.
An estimated 85,000 people are currently turning to ADAP for their
HIV medications. ADAPs serve a very diverse population of people
living with HIV. Almost 80% of ADAP clients have incomes at or below
two-times the Federal poverty level (which only comes to about $18,000
per year for a person living alone). The majority of ADAP clients
are people of color with African Americans making up about one-third,
and Hispanics about one-quarter of ADAP clients. There has been
a 10 percent increase in the number of clients served during the
past year and similar increases are expected in the years to come.
Nationally, ADAP is facing a current budget shortfall of $82 million.
The shortfall is largely a result of several consecutive years of
under-funding compounded by increasing demand and escalating drug
prices. Many state ADAPs across the country are experiencing severe
financial crisis, resulting in limits to treatment access. Recently,
several states have reported turning to some kind of restrictive
measure such as waiting lists. These include Alabama, Georgia, Idaho,
Kentucky, Maine, North Carolina, Oregon, South Dakota, Texas, Washington,
Wyoming and Guam. There are over 600 people on the waiting list
for antiretroviral treatment in North Carolina alone, with an estimated
1000 people on waiting lists nationwide. In addition to waiting
lists, some states have capped enrollment or have placed limits
on the number of prescriptions a client may fill each month. Other
states, including Mississippi and New York, are reporting that they
may be forced to implement restrictions soon.
If the current fiscal crisis continues, states may seek to control
costs in ways that threaten the health of both the program and the
thousands of Americans who rely on it. For example, some states
have delayed adding pegylated interferon, an important new drug
for hepatitis C treatment, to their formularies. The expected approval
next year of T-20, a new class of HIV inhibitor likely to be of
importance to people with multiple drug resistance, will further
stretch ADAP budgets. Some ADAP medical advisory boards are evaluating
dropping certain medications currently provided in order to further
reduce costs. Some states may also be considering requiring co-pays
or medical pre-authorization plans. These measures could put ADAP
services completely out of reach of its most vulnerable clients
and create additional barriers to access for many others.
What is Driving the ADAP Crisis?
- Inadequate federal funding. ADAP has not received adequate funding
increases from Congress the past few years. While ADAP appropriations
increased by 12 percent from 2000 to 2001, the number of clients
increased by 10 percent and the cost of drugs increased by 16
percent during the same period. ADAPs cannot keep pace with rising
costs and service demands at the current funding level.
- Inadequate state funding. Sixteen states do not contribute
at all to ADAP and others provide inadequate contributions. Continued
weakness in the national economy suggests that additional funding
from states that have had more generous programs may be frozen
or even scaled back.
- Increases in drug prices. Monthly drug expenditures by ADAPs
rose by 320 percent from 1996 to 2001. Some of this was due to
adding additional drugs to formularies, but much of the increase
reflects steeper purchase prices. Several drug companies introduced
sharp price hikes at the beginning of 2002, although some have
since announced that they will freeze prices for one or two years
for ADAP programs.
- Increase in outreach and testing programs across the country.
The Ryan White CARE Act reauthorization of 2000 provided for increased
outreach and testing programs with the goal of helping to identify
new HIV infections earlier and facilitate entry into care. The
success of these efforts has translated into increased client
caseloads that current levels of ADAP funding cannot meet.
- Increase in the number of people testing positive for HIV and
seeking ADAP services. New infections continue to occur at a rate
of approximately 40,000 per year in the U.S. Easier testing methods
and more widely available testing has increased the number of
people learning their HIV status, and better service coordination
now ensures that more people are being directed into the care
system offered by ADAP. Furthermore, people now remain in the
program longer because they are staying healthy and living longer
due to the drugs.
What Must be Done to End the Crisis?
Congress must appropriate an increase of $162 million in federal
funding for ADAP for fiscal year 2003 (October 1, 2002 to September
30, 2003). This figure includes the current $82 million shortfall
plus an $80 million increase needed in the next fiscal year to provide
adequate financial relief to ADAP.
The President's goal, as articulated in his FY2003 budget, of reducing
the number of new HIV infections by 50 percent by 2005, cannot be
achieved without a sufficient funding commitment on the part of
the federal government. There is a direct fiscal and epidemiological
relationship between testing, surveillance, care and treatment,
individual longevity, and reduction in new infections. The national
response to AIDS carried out through the various federal agencies
is a linked strategy. Shortfalls in one program area inherently
impact capacity and success in other program areas.
Although funding for the CARE Act has grown over the past ten years,
federal and state funding have not kept up with growing demand for
services. The states' Ryan White care and treatment programs are
safety net programs. They are the payer of last resort and provide
services to those most in need. Without an increase of, at minimum,
$162 million in FY2003, states will be unable to maintain their
existing programs, much less enroll new clients.
The New York ADAP Crisis
New York State is facing a $16 million shortfall in the current
fiscal year due to inadequate increases in the Federal ADAP appropriation
in the Ryan White CARE Act. This means that the projected expenditures
for the year exceed the annual money promised by Congress, and even
by using savings or redirected funds from other state sources to
temporarily bridge the gap, restrictions on access to essential
AIDS/HIV drugs and services are looming.
NY ADAP continues to grow at a consistent rate of more than $20
million a year, due to increasing enrollment (caused by new infections
and people living longer), increasing utilization of drugs and services
(to treat and monitor HIV disease and the side effects of medications)
and ever-increasing drug prices.
NY ADAP has had a moratorium on new drugs and services since November
2000 in anticipation of this pending crisis and has taken measures
to slow growth and accumulate savings that can be used as a short-term
stopgap. However this moratorium has prevented the program from
offering coverage for the new standard of care for hepatitis C infection,
pegylated interferon plus ribaviran.
The moratorium may become critical next year if ADAP is unable
to cover the important new antiretroviral drug T-20, expected to
receive FDA approval early in 2003. A preliminary estimate puts
the cost of adding T-20 to the NY ADAP formulary at about $12 million
the first year. All of these factors add up to an additional $48
million needed for New York's fiscal year 2003.
NY ADAP is redirecting funds from other HIV programs to close the
budget gap this year, and has requested increased funding from the
Title I HIV Planning Councils of New York City, Lower Hudson, Long
Island and Dutchess County. This approach is undermining the HIV/AIDS
infrastructure by drawing funds away from other necessary support
services that persons living with HIV/AIDS need to be able to enter
into care and treatment.
NY's ADAP budget gap threatens significant reductions in services
for 2003. The specific reductions will be identified through a prioritization
process that has already begun. These cost saving measures represent
the deterioration of a health care infrastructure that has taken
years to build, and erects additional barriers to care for some
of the state's most vulnerable citizens with HIV/AIDS.
Possible cutbacks could include:
- Removing categories of drugs or services covered, such as lipid-lowering
drugs or anti-depressants.
- Mandatory dispensing of generic equivalents.
- Establishing a restricted formulary of preferred drugs.
- Expanding prior authorization plans that require approval before
a drug can be dispensed.
- Cutting back of payments to pharmacies and clinics.
- Requiring co-payments from clients to obtain drugs.
- Tightening medical or financial criteria for obtaining services.
- Establishing waiting lists or capping the number of clients
in the program.
ADAP was designed to fill the gap between people who qualify for
Medicaid and those who can afford private insurance. This gap is
widening. In New York, the majority of ADAP clients make less than
200 percent of the Federal poverty level — the group of people
most affected during an economic downturn. Since we have not experienced
this kind of economic climate since ADAP was first created, it remains
to be seen if the steady trend of increasing enrollment will remain
the same or spike sharply up as the crisis deepens.
Call Congress and The White House
Call your U.S. Representative and two U.S. Senators' offices
in D.C. as soon as possible. You can call the Capitol switchboard-toll-free:
1-800-648-3516. You will need to know the name of your Representative
or Senators in advance. Ask to be connected to their office.
If the toll-free number is continuously busy, you can call
the regular number at
(202) 224-3121.
If you need help identifying your elected officials, you
can call Project Vote Smart at 1-888-868-3762 or check out
their website, www.vote-smart.org.
Identify yourself as a constituent. Tell whoever answers
the phone that you are calling to urge the Representative
or Senator to take a leadership role in advocating for a $162
million increase for the AIDS Drug Assistance Program.
Sample message for Congress:
"I am a constituent of Representative/Senator ________________.
I am calling to urge him/her to do everything in his/her power
to get a $162 million increase for the AIDS Drug Assistance
Program in the Fiscal Year 2003 appropriations bill. This
program provides treatment for people with HIV/AIDS who otherwise
wouldn't be able to afford it. I also urge the Representative/Senator
to support the highest possible funding for all other HIV/AIDS
programs."
Please also call the White House comment line. Ask the President
to demonstrate leadership on this issue by letting Congress
know that he supports a $162 million increase for ADAP. Call
the White House comment line at (202) 456-1111.
Sample message for White House:
"My name is ________________ and I live in ______________
(state). I am very concerned that President Bush has not supported
an increase for the AIDS Drug Assistance Program in his last
two budgets. This program is in a fiscal crisis and many people
around the country are on waiting lists for treatment. I urge
the President to take a leadership role by urging Congress
to support a $162 million increase for the AIDS Drug Assistance
Program and the highest possible funding for all HIV/AIDS
programs."
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Sexual Transmission
of Hepatitis C by Edwin J Bernard
Reprinted from AIDS Treatment Update, September 2002
For subscription information: atu@nam.org.uk
or visit www.aidsmap.com
Coinfection with HIV and the hepatitis C virus (HCV) has increased
in the past few years. Until very recently, the major risk factors
for acquiring HCV were thought to be injection drug use (IDU), haemophilia
and blood transfusion; sexual transmission was considered to be
theoretical but insignificant.
Now, however, there is new evidence that sexual transmission of
HCV is on the rise, particularly amongst gay men with HIV. Recent
studies suggest that not only is sexual transmission of HCV possible,
but that being infected with HIV, and/or having certain kinds of
sex, are major risk factors for transmission of the virus.
In June 2002, the U.S. government's National Institutes of Health
issued a consensus statement by an independent panel of clinicians,
researchers and community groups with expert knowledge of HCV. For
the first time, they added sexual transmission to the list of exposure
risks for HCV. Although they continued to say that the risk was
extremely low for heterosexual monogamous couples, they added that
"HCV-infected individuals with multiple sexual partners or
in short-term relationships should be advised to use condoms to
prevent transmission of HCV and other sexually transmitted diseases.
1"
Last month the UK Department of Health issued their Hepatitis C
Strategy for England. The approach of the DoH is similar to that
of their US equivalent. "There is evidence that both homosexual
and heterosexual transmission of hepatitis C may occasionally occur,"
the report states, before offering the somewhat contradictory advice
to people with HCV to discuss the use of condoms with regular partners
and practice safer sex with new partners.
Two large HIV clinics in London have seen an increase in new HCV
infections over the past six months, causing concern that the risks
of sexual transmission for gay men with HIV in particular have been
underplayed. Is it possible that just like the delay that occurred
over public health messages about the current syphilis outbreak
amongst gay men, not enough people are taking the sexual HCV threat
seriously? "I hope it isn't going to take us two years to realise
that yes, it's here, and it's being sexually transmitted,"
says Dr. Sanjay Bhagani, specialist registrar in infectious diseases
and HIV at London's Royal Free Hospital.
Early evidence on HCV transmission
HCV was first identified in 1989 and although studies as far back
as 1993 pointed to sexual transmission as a probable risk factor
amongst gay men, the information did not translate into a public
health message. This is likely because many more studies showed
that the risk of sexual transmission was seen to be extremely low
in the general population, and there may also have been an assumption
that safer sex messages relating to HIV would also implicitly cover
HCV transmission.
In these earlier studies, published between 1993-1996, data on
three different cohorts of gay men without a history of IDU in the
U.S. showed that between 3-5 percent were infected with HCV. Osmond
found that HCV infection was marginally associated with more than
50 sex partners a year; or more than 25 oral receptive partners;
or more than 25 anal receptive partners2. Buchbinder
found that sexual risk factors for HCV infection included receptive
anal intercourse, fisting, having a sexual partner with a history
of IDU, a self-reported history of genital herpes and being HIV-positive3.
Ndimbie found that whilst the number of sexual partners was not
a significant risk factor, a history of syphilis, rectal gonorrhoea,
insertive anal intercourse with ejaculation, and douche or enema
use before anal receptive intercourse were statistically significant
sexual risk factors4.
When Rooney5 undertook a 1998 review of the literature
into sexual transmission of HCV amongst the general population,
he concluded that there was "a small but definite risk of sexual
transmission of hepatitis C" of between 1-3 percent. Rooney
did not look at the difference between heterosexual and gay sex
transmission risks, however.
Since 1998, there have been many studies looking for a heterosexual
transmission risk of HCV in monogamous couples that have found there
is little to none. For example, Sciacca's Turin Study found that
only three out of 196 long-term heterosexual spouses were infected
with the same HCV viral genotype, and concluded that while sexual
transmission of HCV was a possibility, "this method of transmission
does not appear to be important if compared with that of other viruses
(hepatitis B virus and HIV)6." Similar conclusions
were drawn by Garcia7 at the recent International AIDS
Conference in Barcelona.
However, not all heterosexual transmission studies have come to
the same conclusion, particularly those that include casual partners.
Tenegan looked at the sexual partners of HCV-positive blood donors
in Brazil from January 1992 to July 1996 and found that 11.76 percent
were HCV-positive. Sexually transmitted infections (STIs) were found
to be more prevalent among partners with HCV infection, suggesting
that the high prevalence of HCV infection seen here may be attributed
at least partially to sexual transmission because they put themselves
at risk of other STIs.
HCV, HIV and Sex
Though it has been suspected since 1994 that coinfection with HIV/HCV
contributed to a higher risk of HCV transmission than being singularly
infected with HCV (since HCV viral load was shown to be significantly
higher in those coinfected with HIV/HCV8), it was only
towards the end of last year that a study confirmed that HIV/HCV
coinfection magnified the risk of sexual transmission of HCV to
both heterosexuals and gay men.
Researchers from Naples found that HCV infection was almost three
times higher in those who were HIV-positive compared to HIV-negative
controls (15.1% versus 5.2%). Significantly, 18.7 percent of those
who had regular heterosexual or gay sex with an HIV-positive partner
were HCV-positive, compared with only 1.6 percent for partners of
HIV-negative controls. The authors concluded therefore, that "in
subjects who had only a sexual risk factor for parenterally transmitted
infections, HIV may enhance the sexual transmission of HCV9."
At the same time, another study found that HIV, certain sexual
acts, and multiple sexual partners, correlated with a higher risk
of sexually transmitted HCV amongst gay men. Here, 662 HIV-positive
and HIV-negative men in the Vancouver Lymphadenopathy Cohort were
investigated for HCV. Nearly 9 percent of HIV-positive men were
HCV-positive compared with 2.6 percent of the HIV-negative men.
Almost half (49%) of HCV-positive men reported never injecting drugs.
The HCV-positive men were more likely to report the following: more
than 20 sexual partners in the last year; more than 100 lifetime
partners; practicing insertive fisting; practicing receptive anal
sex, and practicing insertive oral-anal sex (rimming). A comparison
of the non-IDU HCV-positive group with the non-IDU HCV-negative
group found insertive rimming and insertive fisting associated with
HCV infection. Multivariate analysis showed three factors independently
associated with HCV infection: injecting drug use; HIV infection
and more than 20 male partners in the last year10.
Three further studies confirming HIV as a cofactor for sexual HCV
infection were reported at the recent International AIDS Conference
in Barcelona. Risbud from India found that HIV infection was independently
associated with more than a three-fold increased likelihood of HCV
infection amongst STI clinic attendees11. Mendes-Correa
from Brazil found that independent risk factors of HIV/HCV co-infection
amongst male and female AIDS outpatient clinic attendees were (highest
risk first): injecting drug use; a sexual partner with past history
of chronic hepatic disease; a sexual partner who had received a
transfusion; age above 30; anal intercourse; use of inhaled illicit
drugs; and a history of an IDU sexual partner12. Finally,
Abresica from Italy found that 20 percent of women who had been
infected with HIV by HIV/HCV coinfected partners were also infected
with HCV, leading the co-authors to conclude: "It's probable
that HIV and its related opportunistic infections of the female
genital tract could strongly facilitate HCV sexual transmission"13.
Increasing UK Cases
Mark Nelson, consultant in HIV at the Chelsea & Westminster
Hospital, London, has been convinced for a long time that HCV is
sexually transmitted. "What we've seen recently is an outbreak
of syphilis (amongst gay men)," says Dr. Nelson, who also runs
the HIV/HCV coinfection clinic, "and with the outbreak, what
we've noted in the HIV clinic are small but increasing numbers of
people seroconverting for HCV. Approximately a quarter of those
have picked up syphilis at the same time, suggesting that HCV is
sexually transmitted."
Dr. Sanjay Bhagani has been running the Royal Free's HIV/HCV coinfection
clinic since last October. "In the last six months we have
picked up six patients who have seroconverted for HCV," he
says. "We've been through all of them with a fine tooth comb
in terms of risk factors and it seems that they have none of the
other risk factors for HCV transmission," leading him to conclude
that sexual transmission was the most likely route. "Two have
an HCV-positive partner, and one had a gonorrhea coinfection,"
he adds, "leaving me in no doubt that these were due to sexual
transmission."
Both clinics only found these new HCV infections because of abnormal
liver function tests (LFTs) since most acute HCV infections are
clinically asymptomatic. "If we weren't doing the LFTs we wouldn't
pick up (the acute infections)," says Dr. Nelson. This is because
although most HIV clinics test for HCV during intake, regular screening
is not commonplace. "Part of the problem is, once you've been
tested you tend not to test again, so we're now promoting yearly
testing for HCV," he adds.
"At the Royal Free we screen first for antibodies and do LFTs,"
says Dr. Bhagani. "If you have persistently abnormal LFTs,
you're antibody-negative for HCV, and your index of suspicion is
high, we do an HCV PCR [viral load test]."
The most common way to measure HCV infection is the ELISA-2 anti-HCV
(antibody) test. However, HIV infection can make the diagnosis of
HCV more difficult since in a small minority, HCV infection may
not show up on antibody tests in HIV-infected people. Last year,
Bonacini found that 5.5 percent of people with HIV tested negative
for HCV antibodies but were positive on the Amplicor™ PCR
test for HCV viral load14.
Dr. Nelson estimates that around seven percent of HIV-positive
patients at Chelsea & Westminster are coinfected with HCV. "A
lot of them have none of the major risk factors of IDU or blood
transfusion," he says. "Clearly a lot of people have tattoos,
so you can't say it didn't come from tattooing, but when we screened
individuals in the GU clinic, a history of tattooing was not a significant
risk factor for HCV. And of course you can't exclude toothbrushes
and razors. But I think the majority is sexually transmitted."
"There is a strong biological probability as to why coinfected
men should be at higher risk of transmitting HCV," continues
Dr. Bhagani. "If you look at the HCV viral loads in people
who are coinfected with HIV, as compared to singularly infected
HCV patients, they are much, much higher. And the higher the viral
load, the higher the risk of transmission."
The jury is still out, however, on the actual mechanism of HCV
infection during sex. Nelson points to a recent study that found
that the higher the HCV viral load, the higher the level of HCV
in saliva15," although we don't really know what
that means," he admits. Many of the studies reviewed here point
to fisting, rimming, and unprotected anal intercourse as being associated
with a greater risk, leading Dr. Bhagani to speculate that "practices
that involve blood may be more high risk."
Safer Sex, Screening, Treatment
Drs. Nelson and Bhagani both believe that people with HIV can best
protect themselves from acquiring HCV sexually by continuing to
practice protected anal intercourse, rimming and fisting. "Like
everything, you're better off not getting it, and since there is
no vaccine available, taking precautions is the only way,"
says Dr. Nelson.
They also strongly suggest that yearly screening for HCV should
become the norm in all U.K. HIV clinics. "The first thing we
really need to know in this country is what is the true prevalence
of HCV in the HIV population," continues Dr. Nelson. "It
is clearly something that people who have got HIV have put themselves
at risk of. We need to make sure that everyone is screened for HCV.
The advantage of picking it up early means you are much more likely
to eradicate it."
Although similar evidence is lacking in those who are HIV/HCV coinfected,
last year, Jaeckel showed that HCV can be eradicated in HIV-negative
people during acute HCV infection after 24 weeks treatment with
interferon alpha. The average time from infection until the start
of therapy was 89 days, suggesting that screening every three to
six months might be optimum for those who believe they are at the
greatest risk of acquiring HCV sexually. In this trial, at the end
of both therapy and follow-up, 98 percent had undetectable levels
of HCV and normal LFTs16. "The data for treating
acute HCV from the Jaeckel paper is using just interferon alone,"
says Dr. Bhagani. "At the Royal Free we use pegylated interferon
and ribavirin since we feel we should be giving these people the
best standard of care that we can."
Eradicating HCV during the acute stage "may be very important
when you look at the data on HIV/HCV coinfection and higher rates
of progression to end-stage liver disease," concurs Dr. Nelson.
Many recent studies have confirmed the link between HIV/HCV coinfection
and accelerated progression to fibrosis, cirrhosis, liver cancer
and liver failure (including those by Martin-Carbonero17,
Bica18, Monga19, Hatzakis20, Soto21
and Garcia-Samaniego22). "Before HAART, everyone
was saying you're going to die of your HIV, don't worry about your
hepatitis C," continues Dr. Nelson. "Now suddenly people
are living, and hepatitis is a major cause of morbidity and death
in many people with HIV worldwide. It's something that we can't
ignore anymore, and it's something that we've got to be much more
proactive about."
Take Home Messages
"I think the take home messages are that HCV is sexually transmissible
amongst gay men and it may be more so than with heterosexual transmission,"
concludes Dr. Bhagani. "So gay men and people with HIV should
always practice safer sex. In coinfected patients, HCV is a particular
concern because of the propensity for faster progression to end-stage
liver disease and complications with drug-related toxicity. We know
from singularly infected patients that HCV is potentially curable
if caught early. And so we should be making an effort to try and
detect and treat early HCV seroconversion."
References
Except where stated, references are from XIV InternationalAIDS
Conference, Barcelona, 2002.
1 NIH Consensus Statement, 10–12 June 2002.
2 Osmond DH. J Infect Dis 1993;167(1):66–71.
3 Buchbinder SP. J Infect 1994;29(3):263–9.
4 Ndimbie OK. Genitourin Med 1996;72(3):213–6.
5 Rooney G. Sex Transm Infect 1998;74(6):399–404.
6 Sciacca C. Panminerva Med 2001;43(4):229–31.
7 Garcia S. abs ThPeC7491.
8 Eyster ME. Blood 1994; 84(4):1020–3.
9 Filippini P. Sex Transm Dis 2001;28(12):725–9.
10 Craib KJP. 8th CROI, 2001: abs 561.
11 Risbud AR. abs WePeB6026.
12 Mendes-Correa MCJ. abs ThPeC7493.
13 Abresica N. abs C11013.
14 Bonacini M. J Acquir Immune Defic Syndr 2001;26(4):340–4.
15 Hermida M. J Virol Methods 2002;101(1–2):29–35.
16 Jaeckel E. N Engl J Med 2001;345(20):1452–7.
17 Martin-Carbonero L. AIDS Research and Human Retroviruses 2001;17(16):1467–1471.
18 Bica I. Clin Infect Dis 2001;32(3):492–497.
19 Monga HK. Clin Infect Dis 2001;33(2):240–247.
20 Hatzakis A. AIDS 2000;14(suppl 4):S5.
21 Soto B. J Hepatol 1997;26(1):1–5.
22 Garcia-Samaniego J. Am J Gastroenterol 2001;96(1):179–183.
Down in the Lab
by Bob Huff
The Human Immunodeficiency Virus (HIV) is a virus that has a detrimental
effect on the human immune system. That much should be obvious from
its name. Virologists study viruses and immunologists study immune
systems, but since HIV came along, more and more scientists from
the two fields are learning about each other's work. In the early
days of HIV research, virologists led the campaign to discover the
virus's vulnerability to antiviral therapy. But immunologists have
not been resting; we're learning more everyday about the secrets
of human immunity and what goes wrong when HIV enters the scene.
The progress of science depends on a continuing flow of detailed
and reliable communications about the latest discoveries, observations
and techniques. Big news in basic science is either held for a big
conference or reported in one of the important science journals
such as Science Magazine or Nature. But smaller
reports of month-to-month progress are typically published in specialized
journals that serve more specific fields of knowledge. For example,
most virologists eagerly await each new biweekly issue of the Journal
of Virology to see what their colleagues are up to.
This article takes a look at the September 2002 issue of the Journal
of Virology to try to get a snapshot of the kind of HIV-related
work deemed significant enough to be included. Of the 58 reports
published in this issue, 13 specifically involve HIV. Other articles
may concern SIV (which infects monkeys) or Feline Immunodeficiency
Virus (which infects cats) as well as a number of other well-known
viruses such as hepatitis C and B. Several of the AIDS-associated
opportunistic viral infections such as CMV and HSV are represented,
as are a host of esoteric but no doubt interesting viruses such
as cauliflower mosaic virus and bovine viral diarrhea virus. But
we're going to stick to HIV.
Keep in mind that most of the work published in this journal is
more provocative than definitive. Usually the experiments were conducted
in laboratory cell lines. Such in vitro studies may initially seem
promising then later turn out to have little relation to what goes
on in living beings. For the most part these papers are part of
an ongoing discussion among workers in the field about what they
have learned. Most of the reports were submitted in the Spring of
2002 and accepted at the beginning of Summer. It may seem insufferably
geeky to want to examine HIV science at this level, but the need
to know what's up is compelling.
Immunity Under the Radar
Most everybody has heard of the two major wings of the adaptive
immune system: cellular immunity (the kind that eliminates infected
cells and the form of immunity that is most directly affected by
HIV) and humoral immunity (the kind that generates neutralizing
antibodies to vanquish invaders). These systems are called adaptive
or specific immunity because they adapt themselves to target specific
invaders. To do this they typically need a little time to get up
to speed. So, before these specialized systems kick in, there is
a grab bag of other tricks that evolution has provided to repel
the first wave of alien invaders. Collectively these are known as
innate or non-specific immunity.
One well-known innate antiviral defense system is the interferon
response. If a cell becomes infected by certain kinds of virus,
it will begin to secrete chemical messengers called interferons,
which then travel through the bloodstream activating interferon
receptors on uninfected cells. These activated but uninfected cells
go through a series of changes that put them into an antiviral state.
If the virus spreads to an interferon-primed cell, its protein-producing
machinery stops dead in its tracks and the cell begins to die. This
response means a dead end to any virus that tries to hijack that
cell for replication.
One circumstance that can kick off the process of interferon secretion
is the presence of double stranded lengths of RNA in a cell. Remember
that DNA is the master molecule used to store an organism's entire
genetic code within each cell's nucleus. A cell's genes are typically
stored as coils of very long, durable, double strands of DNA composed
of chains of nucleotides. Proteins, which are the stuff and substance
of our bodies, are made from chains of amino acids. When a particular
protein is needed, the gene for that protein is exposed and a temporary
copy of the gene's DNA is copied onto a single strand of RNA. This
is called transcription. This copy of the gene, called copy RNA
(cRNA), is delivered from the nucleus to the cell's protein-making
machinery where it becomes translated from a chain of nucleotides
into a chain of amino acids. When translation is complete, the chain
of amino acids folds itself up into a protein and gets to work.
All together, this process is called gene expression.
HIV is somewhat unusual in that it keeps the genes for its proteins
stored in a double strand of RNA instead of DNA. After HIV enters
a cell, its RNA is copied into a strand of DNA by the viral enzyme
reverse transcriptase. This piece of DNA is then delivered to the
cell's nucleus and stitched into the master strand of DNA. Later,
when the cell is stimulated to replicate, the viral genes are expressed
right along with normal host genes and new virus particles are manufactured
and released.
Although in some animals the presence of a double strand of RNA
in a cell can trigger the interferon response, in plants and invertebrates,
a double strand of RNA had been known to stimulate a different kind
of response, called RNA interference. It seems that short pieces
of double strand RNA have the remarkable ability to selectively
and very efficiently thwart the expression of host cell genes that
contain identical, complementary nucleotide sequences. It appears
that the double strand RNA recognizes its cRNA twin, which leads
to a shutdown of the protein-making machinery. In a classic experiment,
a cell modified to produce firefly luciferase (a so-called reporter
gene product that can be made to light up) was injected with pieces
of double strand RNA transcribed from luciferase DNA. The result
was literally like turning off a light.
Because the interferon response set off by double strand RNA is
so powerful, RNA interference had never been observed in mammalian
cells. A breakthrough came a couple of years ago with the discovery
that double stranded lengths RNA shorter than 30 nucleotides did
not set off the interferon response. Soon, through trial and error,
it was found that a double strand of RNA in the neighborhood of
22 nucleotides long could effectively trigger RNA interference in
human cells. These shorter bits of double strand RNA are called
small interfering RNAs (siRNA). RNA interference is rapidly becoming
one of the most important new techniques in the cell biologist's
toolkit because it lets them switch genes on and off to see what
they do. Being able to selectively "knock out" genes like
this promises to revolutionize our understanding of how gene products
interact in the complex environment of living cells.
Calling Interference
In the September issue of the Journal of Virology, a paper
by Glen Coburn and Bryan Cullen of the Howard Hughes Medical Institute
at Duke University describe RNA interference as a possible contributor
to our bodies' innate antiviral immunity. Although HIV does not
produce double strand RNA able to naturally trigger RNA interference,
the scientists report on a potentially therapeutic technique to
inhibit HIV replication via this newly discovered mechanism.
The authors created small interfering RNA strands that corresponded
to cRNA for segments of the HIV proteins Rev and Tat. They then
inserted these siRNAs using transfection techniques into cells capable
of supporting HIV replication. In every experiment, the cells dosed
with siRNA showed dramatic and specific inhibition of HIV gene expression
and replication. (In July, two groups also published reports of
inhibiting HIV replication by inserting siRNAs targeting various
HIV proteins.) Of course this raises a question of whether RNA inhibition
can be used as therapy in people. The challenge will be to develop
a way to safely introduce siRNAs into living cells. It may be possible,
but such research is still in its very earliest stages.
There is also the possibility that RNA interference has been operating
as a component of innate immunity all along. If so, then wily viruses
like HIV may have already evolved a defense to this line of attack.
While a therapeutic application of RNA interference may be viable
down the road, in the meantime, virologists have a powerful new
tool to use to tease apart the intricate web of protein-protein
relationships that exists between HIV and its human host cells.
What they discover may well yield the long-sought secret to defeating
the virus.
Caveolin-1 HIV-0
Here's another report about a naturally occurring process that apparently
knocks down expression of HIV — at least in the laboratory.
Caveolin-1 is a protein usually found imbedded in the lipid sheathing
of cellular membranes and is common to certain types of human cells,
including a few that can be infected with HIV. It's thought that
the protein participates in mechanisms that regulate the transmission
of signals from the cell surface to interior processes. Manuel Llano
and workers in the laboratory of Eric Poeschla at the Mayo Clinic
were curious to see if this protein was involved in helping HIV
assemble new virions and facilitating their budding from infected
cells.
Using transfection techniques to insert genetic material directly
into cells in vitro, the researchers experimentally introduced DNA
for HIV-1 along with either DNA for Caveolin-1 or an empty control
into kidney cells. [Cells supplied with DNA inside the cytoplasm
can process the genetic material and translate it into proteins.
Genetic material can be directly injected or, more efficiently,
packaged into an empty virus that is highly adapted to the job of
introducing DNA or RNA into cells.] After the experimental transfection,
the researchers then measured the amount of new HIV produced by
using a reverse transcriptase activity assay. Unexpectedly, they
found that while control cells continued to process HIV, nearly
all HIV activity had been blocked in the cells expressing Caveolin-1.
They tried the experiment several other times to confirm their
observation, and then tried the same experiment with several different
laboratory strains of HIV. It still worked. Next, they tried the
same experiment using a range of doses of Caveolin-1 and found that
small amounts had a smaller effect than larger amounts, a convincing
demonstration of activity called dose response. They also tried
using a different cell type and using different ways of transfecting
the cells, but the outcome was unchanged. To rule out the possibility
that the inhibitory effect was due to RNA or DNA instead of the
activity of the protein, they performed the experiment using a mutant
piece of Caveolin-1 DNA that could not express the protein. This
corrupted gene for Caveolin-1 failed to inhibit HIV, which supports
the role of a functional protein. At this point they were convinced
that transfecting Caveolin-1 along with DNA for HIV blocked expression
of new virus, but how did it work?
Since a small amount of virus was still being expressed in the
presence of Caveolin-1, they analyzed the HIV being produced to
see if it could still infect other cells. It could, which suggested
that although the amount of HIV expressed was dramatically lowered,
the virus itself was not defective. They also did experiments to
determine if the drop in viral production was due to a toxic effect
of Caveolin-1 on the host cell. But again, the inhibitory effect
seemed specific to HIV since the cells were still able to function
normally. The case for HIV specificity was made stronger by an experiment
showing that cells transfected with Caveolin-1 plus DNA for the
measles virus did not inhibit the production of measles virions.
Finally, the researchers split the Caveolin-1 DNA into several
fragments and tested each one until they found a segment of the
protein that retained full activity. The segment, only about 34
amino acids long, corresponded to a region of Caveolin-1 that is
normally buried within the lipid layers of cell membranes. Oddly,
this part of the protein is not known to have any function other
than interacting with itself or with another similar protein called
Caveolin-2 (which Llano reports also inhibits HIV expression). Whether
this protein exerts its effect on HIV directly or through intermediaries
is unknown.
The author notes that HIV can replicate normally in cells that
naturally express Caveolin-1 and speculates that some mechanism
may compensate to create an environment permissive for HIV replication.
Perhaps when Caveolin-1 is overexpressed, as in these experiments,
the compensatory protein is overwhelmed. This is the perfect job
for using RNA interference as a tool to tease out the interacting
protein functions. Hopefully someone, somewhere, is busily turning
genes on and off, looking for the one that unleashes Caveolin-1's
HIV inhibitory potential.
Show Me a SIGN
There has been a lot of interest in understanding what happens during
the very earliest hours after HIV contacts human tissue. It's thought
that an HIV infection occurring through sexual contact gets its
start in mucosal tissues, and that a particular type of cell, called
the dendritic cell, is the most likely entry point. One impetus
to understanding these early events is to help develop a microbicide
that can block infection at first contact.
Dendritic cells (DC) are often described as sentries patrolling
the frontiers of the body, where outside meets inside along vulnerable
mucosal tissues. DCs are mobile, and they regularly travel from
the mucosal frontier to immunity centers in lymph nodes where they
display samples of the invaders they've met at the gates. While
some DCs express the CD4 molecule on their surfaces, suggesting
that they can be targets for direct infection with HIV, they also
express another cell surface protein than can bind HIV called DC-SIGN.
It is thought that HIV can interact with DC-SIGN and either be internalized
in the cell or simply carried along piggyback as the DC migrates
to a lymph node. But this is like bringing a fox into the henhouse
since it's in the lymph tissue that HIV meets up with its ultimate
target, the T-cell.
Dendritic cells bearing the DC-SIGN molecule are found throughout
rectal mucosa and in parts of the vaginal epithelium, two prime
targets for blocking HIV infection with a topical microbicide. In
their J Virol article, Robert Doms and researchers from the University
of Pennsylvania contribute a few new nuggets to our understanding
of DC-SIGN and offer a new set of tools for future research.
First, the investigators report on a density analysis of DC-SIGN
molecules on the surface of dendritic cells taken from seven volunteers
over several months time. While there was some variability between
and among individuals over time, the count of DC-SIGN molecules
consistently exceeded 100,000 copies per cell. In previous studies
using laboratory cell lines, the authors had determined that about
60,000 DC-SIGN molecules per cell was necessary to support efficient
virus transmission.
The second part of their paper reported on a method of blocking
DC-SIGN by using monoclonal antibodies (Mabs) to effectively reduce
the number of molecules available for HIV attachment. Although the
authors found a set of Mabs able to block virus binding in laboratory
cell lines, these proved less effective at blocking virus transmission
in a model using dendritic cells that had been stimulated from precursor
cells. The authors propose that while partial inhibition of HIV
transmission can be demonstrated by blocking DC-SIGN, there are
most likely other cell surface molecules involved in binding and
transmitting HIV. This paper offers some incremental knowledge about
DC-SIGN and a new set of tools that may help researchers understand
how HIV first interacts with the body. But as the authors admit,
"our understanding of the factors that control DC-SIGN expression
in vitro, and its pattern of expression on specific types of DCs
in vivo, is far from complete."
References
Coburn and Cullen. Potent and specific inhibition of Human Immunodeficiency
Virus Type 1 by RNA interference. Journal of Virology, Sept 2002,
p. 9225–9231
Novina et al. siRNA inhibition of HIV-1 infection. Nature Medicine,
July 2002. p. 681–686
Llano et al. Blockade of Human Immunodeficiency Virus Type 1 expression
by Caveolin-1. Journal of Virology, Sept 2002, p. 9152–9164
Baribaud et al. Quantitative expression and virus transmission
analysis of DC-SIGN on monocyte-derived dendritic cells. Journal
of Virology, Sept 2002, p. 9135–9142.
Tales of a
Housepunk Nothing, Or: I Was a Twenty-Something Outreach Worker
By Rachel McLean
Reprinted from Harm Reduction Communication, Spring 2002
For subscription information: hrc@harmreduction.org
or visit www.harmreduction.org
"No woman is required to build the world by destroying herself."
Rabbi Sofer, 19th Century.
Until recently I worked as an outreach worker/advocate with young
injectors in San Francisco. In the course of those four years I
experienced enthusiasm, martyrdom, burnout, and all sorts of changes
in between. This is my attempt to extract from my experiences ways
that, as providers, we can take better care of each other and ourselves.
My History
My involvement with the street scene started when I was fourteen.
Squatting in downtown San Francisco, I drank, sparechanged and table-dived
with the rest of the homeless punks. But I was still a housepunk;
one of those kidz who talks too loud about the few drugs they do
and still has a job scooping ice cream two days a week. Nor was
I like the kids I worked with later, who'd been homeless for years
on end. I had enough social support to return to and eventually
graduate high school by living with a friend.
By age twenty I had quit alcohol and other drugs and begun working
as an outreach worker for the Haight Ashbury Youth Outreach Team.
I'd been living indoors for several years but some of the people
I'd squatted with were still on the streets and would come into
the drop-in center. Being in a provider role with old friends felt
awkward and difficult. Until I knew better, I dealt with my discomfort
by overzealously attempting to prove that I was still "down."
I eventually realized that 'the kidz' (homeless youth ages 14–29)
could see through my insincerity, and I finally learned to just
be myself — a housepunk.
The Work
Without knowing what it was called, I did everything a good harm
reduction counselor/outreach worker/everything-else-under-the-sun
could do. I met the kidz where they were at: in the park, on the
concrete, high as fuck, numb or happy, twacked on sleep deprivation
or down, down low. I let them hang out at the drop-in high when
other programs wouldn't, keeping them awake to prevent them from
overdosing. I sat by their sides in hospital waiting rooms for hours
on end to ensure they got proper care from oftentimes judgmental
doctors. I listened to horrific stories of pain and abuse, and gave
support; talking about hope, safe shooting, taking breaks. I survived
evictions and agency funding nightmares to defend the kidz against
NIMBYs, and pled with probation officers to keep them out of jail.
I loved those kidz, and became integrated into their lives like
the mother's they never had would've, could've, should've if things
had been different. It was me and the kidz against the world and
I was going to take it all on. On rainy nights I lay awake, struggling
to believe that I was not inherently evil for having a bed to sleep
in when others were cold, unsafe, freezing outside. Early on I was
offered a raise and refused it, saying we should spend the money
on socks. I thought that if I just fought hard enough, things would
be okay. I was a guerilla fighter on the frontlines of the never-ending
battle called harm reduction.
But it was never enough. For every kid off the streets, two came
on, and one was inevitably someone who'd just left the year before.
Operating in an entirely different context than the mainstream,
I had to learn to define success in totally different ways. I soon
learned not to have so many expectations because things didn't always
change for the better. When one of the kidz would die, we'd have
a memorial in the park to remember her. I learned that really all
I could do was love unconditionally and hope that people would stay
alive long enough to realize their own dreams. I gave a million
pep talks to other service providers to remember these things. Yet,
amidst all this non-judgmental, fatalistic serenity, my heart broke
daily.
Burnout
With every overdose, every rape, every stolen backpack, every beaten
up girlfriend, every back-to-town-&-strung-out-again-after-a-year-of-doing-so-damn-good
kid, the grief continued to build. In time I felt like I was going
to lose my shit from the cumulative heartache. We bought a book
for one of the memorials and with every death it just sank in that
the book would eventually fill with the names of kidz and friends,
loved and lost. I began to wonder, not if anyone else would die,
but just who would be next. I obsessed about overdose; hoping to
somehow stop it, rein it in. I felt panicked and traumatized, numb
with constant mourning in the way that I imagine medics feel, bandaging
and burying soldiers on a battlefield. Only this was the War on
Drugs. I was afraid to feel, fearing what would happen if I really
let myself go. I spent Friday nights watching depressing movies,
waiting to release the tears I had been withholding during the week.
After several years of this, I realized that as much as I immensely
valued the relationships I'd taken so long to build, I was no longer
putting my all into the work.
I was exhibiting the classic signs of burnout, "psychic numbing,"
"compassion fatigue" and "post traumatic stress syndrome."*
I felt unable to feel or give anything emotionally. I found myself
hiding in the office, hoping no clients would come in. I would spend
hours piddling around with paperwork, organizing the outreach supplies
closet, attempting to establish some sense of control and order
amidst the chaos around me. When new kidz came to town, I found
that I no longer had the same enthusiasm I'd once had for establishing
rapport with them. I was less and less able to listen to the kidz
I already knew, and quick to snap when they went on and on about
how they were going to change their lives. After years of the work,
I felt like a sopping wet sponge, so saturated with grief that I
could not absorb another drop.
I will never forget this one kid, "Jeffrey" (not his
real name) who told me he only smoked pot and would never touch
injection drugs as long as he lived. Without even realizing it I
said something like, "Yeah, right. That's what they all say.
You'll probably just get strung out and OD like the rest."
I had heard people say that line so many times before and still
get strung out, only in the past I had been able to censor the cynical
reaction in my head. This time however, my cynicism got the best
of me, and my sense of boundaries totally failed. Luckily, Jeffrey
called me on it and I apologized profusely telling him I'd just
seen so many kidz go down hill and it was a hard process to watch.
Jeffrey never did progress to the hard stuff but even if he had,
that comment would have been totally uncalled for. I could have
expressed my concern, and told him what other street kidz had experienced
without treating him like his fate was already written. Although
I sometimes see Jeffrey and we laugh about it, that experience was
a painful wake-up call for me. I saw that I could not continue on
the path I was on; that something had to give.
Thinking about Using
As burnout settled in, I felt overwhelmed by such immense suffering
and sought ways to shut off. For a while all I could think about
was wanting to shoot up. I had been straightedge (abstinent from
alcohol, cigarettes, coffee, and other drugs) for years and had
no experience using heroin. The people I was surrounded by were
not happily moderating their drug use, taking their time to find
a vein in a clean, well-lighted place for shooting up. They were
fucking miserable, and told me so daily. Their lives were marked
by dopesickness, hustling, cops, abscesses, hepatitis C, jail, inaccessible
treatment programs and friends dying. I saw the ramifications of
heroin addiction daily, so why was I at home looking at the phone
thinking, "I could call so and so, she'd show me what to do.
I've got syringes, I know where people cop, it would be so easy..."?
I have heard it said that the mind imbibes the qualities of the
things it contemplates, so it makes sense that I would want to use
when I was surrounded by it every day. I was also a harm reductionist
operating without much support on an agency or community level,
which led to feelings of martyrdom and accelerated the burnout I
was feeling — and contributed to my desire to use. Like so
many others, I had become so identified with the provider role that
I could scarcely take care of myself, or ask for the help or support
that I needed. Nor could I think outside of the box; in my world
the only roles available were of helper and helped. Feeling like
I could not handle being the helper anymore, the only other option
was to do what the "helped" were doing: shooting up.
White Privilege & Survival Guilt
Working as a provider, I wanted to use in order to deny my privilege,
and to "feel the pain" of the kidz. Part of me felt pulled
by the Drugstore Cowboy romanticization of heroin use. Using represented
the forbidden permission to lose control. It would enable me to
absolve myself from responsibility, and simultaneously merge into
the chaos of oneness with the kidz, thus absolving myself of my
white/middle-class/living-indoors privilege. (Or so I thought.)
Shooting up seemed like a viable option, since I had friends in
the harm reduction field who had done exactly the same up once they'd
started doing needle exchange. I envied their release, the street
cred that came with being an out IDU/provider and the manner in
which they were taken care of — in a way that their clients
rarely were — by other providers. Yet, as much as I felt tempted
to, I did not return to old modes of coping. I realized that using
would only decrease my abilities to deal with my own issues and
to help the kidz.
My Role as a Provider
The kidz had peers on the streets; the role that I played was different.
I wasn't someone to rip off, nor someone who would take advantage
of them if they let down their guard. I was someone outside of the
scene that they could trust, because I wasn't like them. I believed
that my role in their lives was to show that it is possible to hold
onto your values, freedom, anarchy, etc., while taking care of yourself.
Using and getting sloppy strung out would hardly have supported
that role. (I know myself — I would've gotten sloppy.) If
anything, absolving myself from responsibility through drug use
would have communicated a message that was contrary to the one I
claimed to teach. If I expected drug users to be responsible for
their behavior, then the same should be expected of me. My starting
to use, however "responsibly," would not have been a responsible
decision. It would be me not dealing with my own problems. I did
not want to use to "get high," although not feeling would
have been an added bonus. I wanted to use to fuck up; to destroy
the life and responsibility that I had created for myself.
Coping Strategies
I worked as an outreach worker for four years, and never used. I
decided that it wasn't an option for me, that I wanted to feel even
if it brought on a flood of emotions I didn't want to face. Choosing
to feel meant I had to find new ways to deal with my burnout. To
cope, I baked cookies, I wrote, I went dancing, I talked to friends,
I watched sad movies and poured myself into my work and school.
For a long time I knew that these things would only tide me over
but that I needed a long break from the work. For personal and programmatic
reasons I felt like it was never the right time to leave. I felt
guilty, like I would be abandoning the kidz to struggle against
adversity alone. Like leaving would mean I was an uncaring sellout,
who wasn't down for the struggle. It had to get to the point where
I just couldn't put off taking care of myself any longer. And it
did.
I quit my job and spent three months traveling in Mexico and have
since returned to take an extended break from direct service work.
It's been a challenge to remember that taking care of myself is
actually the best thing I can do for the world right now but I have
faith that I am doing the right thing. This article has been my
attempt to make sense of my experience, with the hopes that those
still doing the work might learn from them. Is it inevitable to
burnout on this work? Maybe. But I don't believe we should have
to get to the point of no return before we stop to take a break.
There must be better ways of taking care of ourselves while we do
this work. To that end, I offer these suggestions.
- Prioritize taking care of yourself, personally and professionally.
a. Personally, this means staying active in other
areas of your life. Seek out and keep up the things that are fun
and that give you peace of mind. For me this is writing, dancing,
long walks, but most importantly, drinking tea, eating toast and
talking with my closest friends. For you this might be painting,
reading, cooking, doing graffiti, playing sports, bike-riding,
camping, swimming, listening to and playing music, lighting candles,
taking a hot bath, meditating, or any combination of an infinite
number of possibilities. It also means recognizing the signs of
burnout and giving yourself permission to contribute in ways that
are less demanding emotionally.
b. Programmatically, this means providing short
and extended breaks, a realistic workload, decent pay (or if there's
no money, some decent appreciation), clinical supervision, counseling,
mental health days, staff retreats and training. People that take
care of themselves run sustainable programs. For programs with
little funding (i.e., most programs), taking care of staff may
mean providing less comprehensive services, a hard but worthwhile
choice.
- If you're from a privileged background, acknowledge your privilege
and move on. It is important to be an ally to oppressed people
without trying to take on their oppression. The best way to be
an ally is to take care of yourself and make good use of your
privilege.
- If you're using or not, evaluate how you feel about it and go
from there. If your level of use feels good to you, then please
use safely and with company. If not, find support to change it
to a level that feels better, even if that means abstinence. For
some, moderated use is not a realistic option and that's okay.
I believe in harm reduction, and know how revolutionary it is
to believe that users deserve health and dignity. In an ideal
world it would be possible to use without so much harm to the
individual, but we do not live in an ideal world. This is the
real world and not all use is implicitly okay for everyone.
- Dialogue, of course. Talk about what's going on with you, even
if it seems pale in comparison to what you see other people going
through everyday. Talk to your friends, your co-workers. If you
don't feel like you have anyone you can trust to talk to, or even
if you do, check out individual therapy. If it's not provided
by your agency, there are usually sliding-scale programs around.
You may also think about starting a harm reduction workers' support
group
- Keep an eye out for your friends, drag 'em along to your support
group!
I don't buy the racist bullshit line in Traffic where
the Mexican drug czar says that overdose acts as treatment. I'm
not waiting anymore for my friends in the harm reduction movement
to be dead or suicidal to remember to tell them I care and am concerned
about their welfare. No more waiting until I'm too numb to be real
with people before I start taking care of myself. The biggest tragedy
of my own burnout was realizing that I'd become so numb from grieving
for all the ones I'd lost that I was doing a shitty job of being
there for the people that were still alive. So, instead of forever
listing the names of the ones that are gone from my life, whom I
will always love and remember, this is my shout out to holding onto
the ones that are still here. Please, for fuck sake, remember that
loving yourself is the greatest gift you can give to the world.
Now, give away.
This is dedicated to all youth h.r. providers in San Francisco,
past, present and future. HAYOT, ATC, SFNE, UFO, EVRC, G-HOUSE,
DIMENSIONS, HH (RIP), YI (RIP) & HIFY.
| Short Course --Notes
on HIV drugs in development
SCH-C Moves Ahead — Carefully
Schering Plough held a meeting to update community members
about the progress of the company’s novel CCR5 inhibitor,
SCH-C, which is moving through the first phases of clinical
development. The pace of testing has been slowed because of
cautions put in place by the FDA after transient electrical
abnormalities were detected in the heart rhythms of three
patients receiving SCH-C at high doses. The abnormality, a
prolongation of the QTc interval, indicates an event when
the heart is signaled to beat before the muscle is fully prepared
to contract. This condition can possibly result in the heart
losing its ability to move blood, with sudden death the outcome.
Because of this potentially catastrophic consequence, the
FDA has asked for close monitoring of patients receiving SCH-C
until the significance of this observation is clarified. Patients
entering the phase Ib trial will probably be observed for
a week or so under constant telemetry in a medical facility
to assure that any arrhythmias are safely detected and corrected.
Interestingly, very little is currently known about the normal
prevalence of QTc prolongation among the background population;
indeed, in the SCH-C study, 3 of 18 patients receiving placebo
also experienced abnormal QTc. Yet prudence (and the FDA)
demands that early studies of this promising drug proceed
carefully and deliberately.
Bermuda Triangle
As expected, Triangle Pharmaceuticals has submitted data on
its nucleoside analog FTC (Coviracil) to the FDA for approval.
They should hear in a month or so if it will receive a priority
review. But this good news was preceded by a report that one
of the company’s other drug candidates, DAPD, has received
a go-slow order from the FDA because of some belatedly noted
findings on the lenses of the eyes of trial participants.
The drug is a nucleoside analog with the attractive potential
to remain active against virus resistant to AZT and 3TC (and
FTC?). During animal testing at extremely high doses, the
drug crystallized in the kidneys, which set off a cascade
of toxic events that included development of corneal opacities.
On the basis of this finding, the company added opthalmologic
testing to their ongoing clinical studies. In a few people,
investigators reported finding minor lens abnormalities, although
no evidence of kidney toxicity that would have precipitated
them. Since there were no baseline eye tests, it’s unclear
at this point what significance these pinpoint spots have,
if any, since similar lens abnormalities tend to become common
with increasing age and UV exposure. But once again, in the
interest of safety, the FDA has asked that new enrollments
into the ongoing trials be temporarily held until more thorough
baseline screening procedures can be put in place.
Although this latest situation is probably not drug-related,
Triangle has had a long string of bad luck with its attempts
to get an AIDS drug into the market. But you can’t say
they’re dodging the reality of their situation. The
company’s web site (www.tripharm.com)
prominently features a list of “risk factors”
on its front page that makes for chilling reading. Check it
out.
Hepsera (adefovir for HBV) Gilead Sciences,
having failed in its attempt to launch adefovir dipivoxil
as an HIV drug due to kidney toxicity at necessary doses,
regrouped its forces and is on the verge of seeing the drug
approved — at a much more tolerable dosage — for
treating chronic hepatitis B infection. The company announced
that it has selected Hepsera™ as the U.S. trade name
for adefovir. Approval should be granted by the time you read
this.
|
Global Treatment
Update
By Bob Huff
Large Mining Companies Decide to Treat
Three large mining corporations active in HIV-ravaged Southern Africa
have announced plans to offer antiretroviral treatment to all of
their employees. The companies, Anglo American, Anglo Gold and De
Beers are among the largest private employers in Africa, and HIV
prevalence rates in countries where these companies operate, Botswana,
Namibia, South Africa and Zimbabwe, are among the highest in the
world. Anglo Gold estimates that 28 percent of its South African
employees are infected.
The announcement said that the program would be rolled out during
the coming year with treatment delivered from existing company-sponsored
clinics. Dependents will not be covered by this first phase of treatment,
although De Beers has said it will extend treatment to a single
sex partner of a worker.
The announcement is a victory for activist and labor groups that
had been pressing for treatment access. Their attention now turns
to other large mining companies in the region, such as Gold Fields
and Harmony, who are still resisting offering treatment to their
employees.
Protest Against Coca-Cola Planned
The presence of the Coca-Cola logo is nearly ubiquitous in Africa.
But despite the company's dependence on a huge low-wage work force
to distribute its product, Coca-Cola has so far refused to pay for
HIV treatment for more than the top echelon of its employees. Coke's
policy is that only HIV-positive people among its administrative
staff are eligible for access to treatment. This leaves almost 100,000
bottlers and distributors without access to medicines should they
become sick with HIV/AIDS.
On October 17, a Global Day of Protest has been planned to draw
attention to Coke's fundamental obligation to implement comprehensive
HIV/AIDS workplace programs and policies, which include treatment
and care for infected workers and their dependents. Demonstrations
are planned in the U.S., Thailand, South Africa, Morocco, and France.
For more information: www.healthgap.org
Pan African Treatment Activist Group Meets
On August 22nd, HIV/AIDS activists from 21 African nations met in
Cape Town to organize a Pan-African treatment activists movement
to fight for access to affordable AIDS medicine and to create an
African voice to talk to international organizations about the AIDS
crisis.
"We are the ones who are suffering, but we are not taking
up leadership roles in the fight against AIDS," said Mohammed
Farouk, coordinator of Nigeria's AIDS Alliance. "It is time
we Africans got together to assert ourselves."
Among the group's goals for itself:
"Develop a community-based response to the AIDS pandemic in
Africa that places PLWAs at the center and ensures the involvement
of PLWAs in key decision-making processes that will affect their
lives."
"Mobilize our communities, our political leaders, and all
sectors of society throughout the continent to ensure access to
ARV treatment for all who need it, starting with the immediate implementation
of the WHO goal to ensure ARV treatment for at least three million
people in the developing world by 2005."
WHO's on First
The World Health Organization (WHO) held an initial meeting in Geneva
to begin setting up global partnerships and creating a framework
for national planning, budgeting and implementation towards their
goal of treating three million people within the next three years.
They hope to have a "blueprint," a "roadmap,"
or some other metaphor for a plan ready to show by December 1 of
this year.
Rapid Tests
will Save Lives
By Gregg Gonsalves
As the cover story in this month's Treatment Issues shows,
the haves and have-nots in this epidemic need not be separated by
oceans and continents. The crisis in funding for the AIDS Drug Assistance
programs may soon deprive thousands of U.S. residents of the drugs
they need to save their lives. Of course, this disaster need not
happen if Congress appropriates $162 million for the ADAP program
for the next fiscal year. Will our members of Congress abandon the
neediest people with AIDS in their own states? The answer is uncertain
and the equivocation of politicians on this issue is indeed sickening,
both literally and figuratively.
Another drama that upsets our notion of have and have-nots in the
epidemic is quietly unfolding in Atlanta and Washington, D.C. Over
the past few years, rapid and simple tests to diagnose HIV infection
have been developed and widely deployed in Africa, Asia and Europe.
These rapid HIV tests can offer an HIV diagnosis in less than half
an hour and can be performed by anyone with a bit of training —
no laboratory is necessary to use these truly revolutionary new
technologies. With up to 40 percent of people who take the conventional
test never returning for results and with a critical need to bring
mobile testing and counseling to overlooked populations, rapid tests
are the key to a new era of HIV prevention.
However, rapid HIV tests have not been available in the U.S. because,
until recently, no company had asked to market one here. One reason
is that the big diagnostic test manufacturers who sell rapid tests
elsewhere in the world are worried about upsetting the market for
their slower, lab-based assays. But this year, a small company,
Orasure Technologies, applied to sell a rapid HIV test in the U.S.
Orasure's application is now before the FDA, which is reviewing
the data and is expected to make a decision soon.
Here is where things get complicated. Unlike AIDS drugs, several
different agencies have jurisdiction over the fate of rapid tests.
The FDA will review safety and efficacy data, just as it does for
pharmaceuticals. But with rapid tests, the Center for Medicaid and
Medicare Services (CMMS) gets to weigh in on how these tests will
be used. What is at stake here is whether Orasure's test will be
classified by CMMS as "moderately complex" or be a "waived"
test. A "moderately complex" label will drastically compromise
the revolutionary promise of rapid testing by mandating that only
qualified laboratories or laboratory personnel can offer these assays.
If community based organizations want to use these tests in-house
or as part of enhanced prevention outreach strategies, they would
have to bring laboratory personnel on board, as well as comply with
a set of onerous rules and regulations that come with the "moderately
complex" designation. If Orasure's test receives a waiver,
it can be more broadly and less restrictively used.
The opposition to giving Orasure a waiver is largely coming from,
you guessed it, laboratory personnel, laboratories and their fellow
travelers within CMMS, which see rapid testing as a threat to their
hegemony over HIV diagnoses and the funding that comes with it.
Rapid testing cuts out the need to send your HIV test to a lab for
analysis and the laboratory middlemen are hopping mad. The lab lobby
is claiming that rapid tests are far too complex to perform without
expensive laboratory support — even though they are being
used successfully in remote villages in Africa right now. They claim
that there will be insufficient oversight, training and quality
assurance for these tests — although HIV testing in the U.S.
is already highly regulated and there is broad agreement that training
and quality assurance programs need to go hand-in-hand with the
implementation of these technologies in the field.
Every year in the U.S., 700,000 people do not come back for their
HIV test results. How many of these eventually walk into an emergency
room with PCP but could have been saved if we could offer test results
in 20 minutes instead of a week's time?
There is nothing standing in the way of rapid testing in the U.S.
but greed and bureaucratic intransigence. CMMS should "waive"
Orasure's test when it receives FDA approval and stop this nonsense.
They were told as much this month by a panel of experts at a consultation
sponsored by the CDC in Atlanta, which brought together all the
parties interested in the fate of rapid testing. The deployment
of rapid testing in the U.S. has been delayed and delayed again.
It's time to get moving.
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