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Past Issues
Volume 19, number 1/2
January/February 2005
The New York "Super Virus"
Who set off the alarm? And why?
Surviving the "Super Bug"
An open letter to gay and bisexual men from GMHC
Men, Meth and Sex
Capsule summaries of recent journal articles
Feminization of AIDS
Chinua Akukwe on choices facing African leaders
The 12th Retrovirus on the
Web
· Webcasts bring
latest HIV science to your computer
· Basic Science
Beckons
· Building a Better
PI
Enter the Supertramp
Daniel Raymond proposes new partnerships in prevention
One Is the Loneliest Number
by Bob Huff
A group of HIV/AIDS community doctors and organization leaders
gathered at the New York City Department of Health and Mental Hygiene
on a Friday morning in early February 2005. They had been summoned
by Health Commissioner Thomas Frieden to attend a press conference
about a newly diagnosed strain of HIV. In a briefing to the group
before the press was ushered in, the commissioner explained that
a gay New Yorker in his 40s had become infected in October 2004
after bingeing on crystal methamphetamine and having sex with hundreds
of people over a period of several months. The man started feeling
sick in November and went to his doctor. By December he was confirmed
HIV-positive and had already experienced a dramatic loss of CD4+
T cells, which pushed him into the range of AIDS. By February his
CD4 count was well below 50. Furthermore, the group was told, he
had a particularly aggressive strain of HIV that was resistant
to every antiretroviral (ARV) drug except Fuzeon. Frieden concluded
these facts were so unusual and alarming that they warranted issuing
an alert to doctors and holding a press conference to announce
that a new, highly virulent strain of HIV was on the loose in New
York City.
Frieden targeted gay men in particular: "It's a wake-up call to
men who have sex with men, particularly those who may use crystal
methamphetamine. Not only are we seeing syphilis and a rare sexually
transmitted disease — lymphogranuloma venereum — among
these men, now we've identified this strain of HIV that is difficult
or impossible to treat and which appears to progress rapidly to
AIDS."
The press reaction was swift and predictable: "AIDS Super Bug," blared
the New York Post; "rare and deadlier form of AIDS," announced The
New York Times. Soon it was on CNN and the nightly
news. "A frightening, never-before-seen ‘superstrain'... full-blown
AIDS sets in with lightning speed." The report sped around the
globe: "New AIDS Peril Puts America on High Alert," announced The
Hindu and other international papers. Yet behind the headlines,
accounts of the "supervirus" were mostly superficial.
Hotlines at AIDS service organizations began buzzing with anxious
questions: "Does this mean my HIV test was no good? Does this mean
my drugs won't work anymore?" People were certainly talking, but
what was the hubbub about? Chatter on the e-mail networks of people
who follow AIDS research immediately zeroed in on one glaring detail:
There was only one case. An unusual and tragic set of circumstances,
no doubt, but, so far, found in just one person. If there had been
a cluster of several cases where people were progressing to AIDS
with a highly virulent strain of untreatable HIV, that would have
been big news. But did a single case warrant a press conference
that launched headlines around the world? As the story filtered
out and the personalities behind the news became known, some pieces
began to fall into place.
Super Ego
The next red flag went up when it was learned that the patient
had been referred by his doctor to a special research group at
the Aaron Diamond AIDS Research Center (ADARC) known for studying
people in the earliest stages of HIV infection. The director of
ADARC is Dr. David Ho, Time magazine's Man of the Year
for 1996 for his role in helping usher in the era of highly active
antiretroviral therapy, or HAART. Dr. Ho was also a chairman of
the Retrovirus Conference, the most important AIDS science meeting
of the year, which was due to open in Boston in two weeks. Many
observers became suspicious because Dr. Ho has a history of announcing
dramatic findings to the press around the time of scientific conferences.
He also has a history of being wrong and overhyping his findings.
In 2002 he announced, to much ballyhoo, that he had discovered
a long-sought natural defense against HIV produced by CD8 cells.
That finding was recently retracted in Science magazine. And at
the 1996 International AIDS Conference in Vancouver, Ho grabbed
hopes and headlines when he posed the possibility of complete eradication
of HIV from the body using the new protease inhibitors. Those dreams
were dashed within the year. Upon hearing of his involvement in
this new sensation, many AIDS insiders immediately suspected the "supervirus" was
Ho's "conference surprise" for 2005.
Super Script
To others, the story simply seemed queer on the face of it. Although
very rapid progression to AIDS is rare, a quick literature search
will turn up several cases where individuals had become infected,
developed AIDS, and died within six months. The average time
to AIDS in untreated persons is usually put at around 10 years.
But, as with any bell curve, there are a few people at each end
of the spread. Some never develop AIDS, while some go quickly.
Rapid progression on its own was not news.
But this patient had a virus that was resistant to drugs in three
of the four classes of antiretrovirals. Wasn't that alarming? Well,
it should be, but it is not uncommon. Studies have found resistance
to at least one drug in 6 to 15 percent of recently infected people.
Even triple-class drug-resistant HIV was found to be transmitted
in about 1.3 percent of new infections, according to one study.
In the corridors of the 12th Retrovirus Conference, in Boston,
several clinicians confided that they had a number of patients
with this extent of drug resistance.* Among people already on therapy,
studies have found at least one resistance mutation in nearly 80
percent of those with detectable viral load.
Frieden claimed it was the unprecedented combination of rapid
progression with transmitted multidrug resistance that justified
the alert. But even this was not unique. In 2001, Julio Montaner
of Vancouver, Canada, reported on two cases of multidrug resistance
in patients who had rapidly progressed to AIDS. Clearly this situation
had been seen before — and the sky didn't fall in — so
what possessed Frieden to unleash a torrent of fear and confusion
over this case? Had he been duped by the fame and authority of
Dr. Ho? Was it all orchestrated by Dr. Ho's public relations firm?
Was Frieden, who has worked in India, so naïve as to think the
global press wouldn't whip this story into a superheated frenzy
far beyond the boroughs of New York? Or did the aggressive commissioner
simply spy an opportunity to advance his own agenda of shaking
up New York's complacent gay community about the unabated AIDS
crisis among them?
New Yorkers could use a wake-up call. Gay men continue to lead
the categories of the newly infected in New York, and alcohol and
methamphetamine use have been shown to strongly increase one's
risk of infection. Take this individual — by all accounts
a successful business executive: How can it be that a gay man with
an active sex life remains uninfected until his mid 40s, then stumbles
in such a dramatic way? Unfortunately, there is nothing unique
about this aspect of his case. Not enough attention has been given
to midlife gay men and they stress they experience. But with shrinking
federal funds for HIV prevention efforts and a shifting emphasis
toward secondary prevention (prevention efforts aimed at reaching
infected people in a medical context, an approach lately promoted
by the CDC as it retreats from funding prevention in high risk
groups) and away from primary prevention education for people at
risk (youth, women of color, and amphetamine users, etc.), men
like this are less likely than ever to have somewhere to turn for
help.
Super Vision
Commissioner Frieden has been admirably successful in his campaign
to curb smoking in New York. Most agree that the quality of life
in the city has improved (although health benefits may take longer
to show up). He has a reputation as a public health activist
but also for being a bit of a Napoleon when it comes to going
after his goals, harboring little patience for criticism or community
input. A look at the medical articles he has authored shows a
long-standing concern with the need to control outbreaks of disease
without trampling civil rights. Frieden made his bones by fighting
tuberculosis — specifically, an outbreak of multidrug resistant
TB that appeared in New York in the early 1990s. TB is a highly
communicable disease and is easily spread in institutional settings
such as hospitals and shelters. Conceivably, you could get it
from standing next to someone in an elevator. The TB treatment
model is classically authoritarian. When a TB outbreak occurs,
the health department swoops in with medical detectives who track
down everyone who may have been exposed and puts the infected
on directly observed therapy (DOT), where a medical professional
watches each pill go down. It's a very effective way of dealing
with an isolated outbreak of TB. But can such an approach work
for HIV?
HIV is relatively difficult to transmit sexually, although certain
practices, such as unprotected anal intercourse, can increase the
risk greatly. Once acquired, HIV is normally a slow-moving disease.
A person who is newly infected may not realize it, or may have
symptoms of acute infection that range from muscle aches to a dramatic
rash and flu-like symptoms. After the initial stage of infection,
an individual's immune system usually kicks in to bring the HIV
under partial control. But HIV replicates rapidly — a new
generation is born nearly every day — so within a few weeks
of settling into its new host, the virus is evolving and beginning
to escape immune control. By the time a year has passed, the dominant
virus may be quite different from the virus a person received at
infection, having gone through the equivalent of 6,000 years of
human evolution. Antiretroviral therapy can knock down the HIV
replication rate to nearly — but not quite — zero. There
are always a few cells hanging around that hold some virus in reserve.
If the drugs are interrupted or stretched too thin, these few viruses
will start to increase in number. The longer the virus is allowed
to replicate in the presence of the drugs, the more likely it becomes
that a random mutant capable of thriving despite the medication
will be generated. Before long, if this keeps up, a drug-resistant
strain is born. The fact is: Most people with multidrug resistance
have made it themselves.
The best guard against resistance is to maintain strict adherence
to effective medication, but it's hard to do. The DOT approach,
from the TB world, has been successfully used to administer HIV
drugs as well. But TB is curable within months, while HIV requires
lifelong treatment. Studies of ARV therapy in prisons have produced
excellent levels of adherence and viral suppression. But it should
be obvious that such means are not solutions for this situation.
The terms "superbug" or "superstrain" are sensational words invented
by the media to sell newspapers. But there are a couple of other "super" terms
that have been conspicuously missing from discussions about the
New York patient. One is "superspreader," an informal epidemiological
term used to describe an individual who is responsible for a high
number of transmission events in a population. Recently infected
people typically have extremely high viral loads. They may also
have a virus that is well-adapted to transmission — after
all, it was recently transmitted to them. Put this person in a
social setting where he is bingeing on drugs and unprotected sex
with multiple partners in weekend-long parties and he will be much
more likely to infect other people than a party pal with a relatively
tame chronic infection. The Hollywood horror angle to this scenario
is that the "superspreader" may have no idea he is infected.
Maybe this is who Tom Frieden really wants to reach. If you can
diagnose people when they are most infectious, then perhaps the
unrelenting cycle of HIV transmission among gay men can be arrested
and reduced. For someone who has tackled outbreaks of TB, it makes
sense. But will it work for HIV? By the time someone has visited
a doctor with symptoms of primary HIV disease and has been confirmed
positive, the most infectious phase may be nearly over. So the
disease detectives from the Department of Health hit the streets
to find anyone our superspreader may have infected (they also want
to find out who infected him and trace those contacts as well).
If they can reach one of his infected contacts early enough, then
maybe the superspreader cycle can be broken. It's certainly worth
a try. But when partners are anonymous or dimly recalled after
drug-fueled lost weekends, it may be tough to make the connections.
In the case of the New York patient, the word is that two of the
people who may have infected him have been contacted, and one is
cooperating with the health agency.
Super Trooper
Contact tracing in New York is voluntary, but notorious cases like
this one always revive fears of more draconian measures. There
is a long list of reasons why compulsory contract tracing is
a bad idea, but some minds naturally run to coercive solutions.
First, any approach that increases HIV stigma or applies the
taint of criminality to people's sexual desires will likely drive
them further away from doctors and support. A better idea is
to get people out of dark, anonymous situations and into testing
and care — not leave them cowering in fear as their health
and sanity deteriorate. But within days of Frieden's announcement,
conservative blogs and talk radio were crackling with calls for
the quarantine and criminalization of drugged-up, gay-sex-crazed
superfreaks. It seemed like 1985 all over again. This is not
to say that frustration over the never-ending epidemic and irresponsible
behavior hasn't riled folks within the gay community too. Syndicated
gay columnist Dan Savage proposed treating viral donors like
deadbeat dads, holding them responsible for the financial burden
of antiretroviral therapy for the people they infect. A letter
to the San Francisco Bay Area Reporter, a gay weekly, simply
recommended locking them up and throwing away the key.
But HIV-negative people are not the only ones at risk. Another
unspoken "super" in all of this is "superinfection." This is a
much misunderstood medical term for acquiring one HIV infection
on top of an existing infection (super, in Latin, means "above," not "faster
than a speeding bullet"). Reinfection might be a less loaded term.
Some people in the HIV community absolutely deny the possibility
of superinfection, probably because it threatens a perceived freedom
to have unprotected anal intercourse with other positive people,
a practice called serosorting. There are theories and a few persuasive
studies that say having HIV is protective against infection with
a different strain of HIV. Nevertheless, there is incontrovertible
proof that superinfection does occur. The worst-case scenario,
of course, is if a person on ARVs with fully suppressed HIV becomes
reinfected with an untreatable, multi-drug resistant strain of
HIV that takes over and plunges him into AIDS. Superinfection has
been convincingly detected in several individuals and in a few
longitudinal studies. The question now is how often, how likely,
and how clinically relevant these events are. One study described
at the 12th Retrovirus Conference calculated that reinfections
may occur as often as initial infections. So a multidrug-resistant
strain of HIV being passed around is a potential problem for both
negative and positive people.
One new tactic Frieden is using to tackle resistance is to demand
that every diagnostic laboratory in the country notify his department
whenever a multidrug-resistant specimen turns up that has originated
in New York City. They have asked labs to be on the lookout for
not only the specific strain that caused the panic but also for
every instance of HIV with a more broadly defined set of resistance
mutations. So far nothing has turned up, although it is not clear
if the labs are taking his request seriously.
To some it seems the commissioner is chasing a utopian fantasy
of monitoring the care of every HIV-positive New Yorker from his
downtown command center. But how will this help prevent new infections?
Frieden's department currently collects HIV viral load and CD4
count reports from the labs, but this information is rarely reported
to the community, where it might make a difference. The city's
HIV testing reports are still running a year behind real time.
If the disease detectives are not swamped with processing these
new resistance reports, they may occasionally hit upon a recent
seroconverter and make an effective intervention. But these are
likely individuals who should be the focus of prevention efforts
anyway, whether they have acquired a drug-resistant strain or not.
A better way to reach these people, it seems, is to create more
opportunities to access medical care, train more doctors to suspect
HIV, take better sexual histories, and perform more tests. This
will require resources and education.
Increasing the rate of HIV testing within the city is another
top agenda item for Frieden. The number of newly diagnosed people
with HIV reported by the city has dropped by 38 percent from 2001
to 2003. But it is not clear whether this reflects a real drop
in new infections or merely a failure to offer HIV testing outside
of the easiest-to-reach populations. The large proportion of individuals
(28 percent) who are diagnosed with AIDS at the same time they
find out they have HIV suggests that HIV tests are either unavailable
or not offered to far too many people. But Frieden has been heard
to opine that the way to increase testing is to lift the barriers,
particularly the requirements for thorough pre-test counseling
and informed consent. While testing procedures could certainly
be streamlined, many would see testing without consent as an unacceptable
erosion of privacy in a land that still bars infected foreigners
from entering the country. As demonstrated by the reaction to Frieden's
announcement, stigma lives in the United States, and mistrust of
government and insurance companies, plus the increasingly insecure
health care situation leave many ill at ease. Unfortunately, there
are still good reasons why testing for HIV is not like testing
for anemia.
Strained Logic
So was this strain of HIV really that special? Almost all transmitted
viruses use the CCR5 coreceptor to gain entry to a new host cell.
CCR5-using HIV is most commonly found during the early years
of infection, but in some people, the virus eventually switches
and begins to use another coreceptor, CXCR4. The switch to using
CXCR4 is associated with a much more rapid loss of CD4 cells
and progressive disease. Ominously, the New York patient appeared
with a virus that could use CXCR4 only a few weeks after his
infection. Also, it is generally thought that drug-resistant
HIV is less capable of replication than the wild type and therefore
more difficult to transmit. But this virus had a replication
capacity equal to or better than the average wild-type virus.
These facts, more than the drug resistance, make this a curious
and unsettling case.
While Frieden put most of the emphasis on the viral "strain," many
HIV scientists who heard about the patient that Friday afternoon
immediately suspected the explanation likely lay with the individual: "More
often than not, [rapid progression] has something to do with the
person infected; not the virus itself," said Anthony Fauci, perhaps
the only AIDS scientist better known than Dr. Ho. Some people are
genetically more susceptible to HIV and disease progression than
others. Yet of the 20 or so immunological characteristics known
to be associated with AIDS onset, this person had none. That does
not mean that some other factor wasn't responsible. New interactions
between the host and the virus are reported almost every month.
One telling aspect to this case was that the patient apparently
failed to mount any significant immune challenge to the infection
and that his CD8 cell count fell along with his CD4 count. But
again, there is no way of knowing if this was due to the virus
or the person.
Some people initially speculated that crystal meth had played
a role in wearing down the man's immune system or somehow revving
up the virus. But there is nothing solid in the medical literature
that points to this, although the patient's reported 20-pound weight
loss during that period might just as well be attributed to crystal
meth use as to AIDS.
So, agendas aside, there were some strikingly unusual and alarming
aspects to this case. It certainly must have seemed that way to
Martin Markowitz, the researcher at Aaron Diamond who evaluated
the patient. After the story broke and criticism began swirling
about the decision to go public, Markowitz spoke before a group
of New York physicians, where he described the patient and distributed
a draft of an op-ed piece he had written about the new strain,
which he compared to "a silent tsunami." An attendee at the meeting
recalled that the researcher was adamant about the significance
of the case and accused the doctors of "looking for a horse" when
faced with a stampeding "herd of zebras." Markowitz subsequently
attended the Retrovirus Conference, where a special session had
been called to discuss the case, but left the presentation to Dr.
Ho, who, it became clear, had been unaware of many details of the
case (such as whether the individual had ever injected methamphetamine — we
were later told he hadn't). So the question remains: Is this case
the tip of the iceberg of some new, highly virulent strain of HIV
that is spreading even as you read this? Or was it a perfect storm
involving an unusual (but hardly unique) case that became supersized
by runaway imaginations, inflated egos, political opportunism and
a gullible press? Was the brouhaha over this individual simply
a heavy-handed way of getting the attention of New York's doctors
and at-risk communities? Dr. Frieden and other health department
representatives have repeatedly said it would have been irresponsible
not to announce the case.
Whatever the merits of the decision to launch this story around
the world, the fact is that, in New York at least, a few more people
are talking about HIV and the reality that gay men still become
infected every day. Hopefully, some are learning that adherence
can prevent drug resistance and that condoms can prevent new infections.
But with all the noise about this virus, how many have learned
to recognize the symptoms of primary HIV infection?
One wonders: If this particular virus of mass destruction does
not exist, did it have to be invented as a pretext for a renewed
war on AIDS? If the only way to get the gay community's attention
is by hitting us in the head with the two-by-four of an imaginary
supervirus, then do the ends justify the means? I suppose it depends
on what comes of all this. Fear has never been demonstrated to
be a sustainable prevention aid. Most agree that clear information
and enlightened self-interest work better. Dr. Frieden has stimulated
some discussion here in New York, and he may uncover some interesting
facts about drug-resistant HIV in the city as well. Over the coming
months he will roll out his plan for tackling HIV in New York City.
Hopefully, all this will result in a net reduction of new infections
when his department reports its estimated HIV incidence numbers
next year.
* It turned out that his virus was phenotypically susceptible
to efavirenz and delavirdine. At last word, he was being treated
with a multidrug combination and his viral load had dropped.
"Super Virus" Timeline
Mid 40s, gay male living in New York City
Five negative HIV tests by private physician between September
2000 and May 2003
May 2003: Tested negative
October 2004: Engaged in unprotected anal sex/ used crystal
meth/2 episodes as a bottom
Late November: Felt sick
December: Visited doctor
Late December: Tested positive
January 2005: AIDS diagnosis
Early January: Referred to ADARC
Mid January: Virologic reports MDR and X4 virus
Jan 22: NY DOH notified
Jan 27: DOH interviews patient; contact tracing begins
Feb 4: Frieden sensed that "something was different"
Feb 7: Conference call with CDC
Feb 9: Frieden talks with CDC head Julie Gerberding; Mayor
Bloomberg briefed
Feb 10: Some community organizations briefed
Feb 11: Alert sent; news conference held
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Squashing the "Super Bug"
An Open Letter To Gay and Bisexual Men
From Gay Men's Health Crisis (GMHC)
In the United States, recent media attention about a multi-drug
resistant HIV (the "super-bug") couldn't come at a worse time — when
HIV prevention efforts are both increasingly censored and under
funded. Unfortunately, many public health officials are currently
relying on a one-size-fits-all approach to preventing further transmission
of HIV. Abstinence is promoted over more comprehensive sex education
approaches that address contextual as well as individual level
factors. There is plenty of research showing the strong link between
important contextual factors — HIV/AIDS stigma, homophobia,
class, racism, community cohesion, depression, substance use, etc — and
individual level HIV risk.
Facts:
- HIV infections with drug resistance (and even multi-class
drug resistant HIV) are not a new phenomenon. In the US and in
Europe 8–20% of all new infections are one-class drug resistant,
and 1–4% are multi-drug resistant (it is higher in men who
have sex with men).
- It's well established in large studies that although 'average'
time of progression to AIDS after initial infection is 10–12
years, there are many cases where people progressed rapidly (within
2 years). Without additional case validation, it is impossible
to scientifically conclude that increased viral virulence, and
not host immune factors or some combination of the two, is responsible
for rapid progression.
- Three conditions must be met before there is serious cause
for alarm: multiple cases have to be shown to be virologically
related; rapid progression must be linked to the virus itself
and not host genetics or weakened immune system (i.e., due to
drug use); and the virus must be readily transmitted.
Reflection:
Fear campaigns launched on the backs of gay men are not new in
the 24 year history of the HIV/AIDS epidemic. What remains crucial
is that we retain control over our bodies and health during these
times. Men who have sex with men, gay identified or not, must
be supported in our efforts to live satisfying and healthy sex
lives, which must include consistent employment of effective
safer sex and risk reduction strategies. We must work to reinforce
as social norms in our community both sex with the minimal exchange
of bodily fluids and condom use whenever possible.
For those of us living with HIV, it is vital that we have access
to and adhere to treatment. For those of us who are HIV negative,
routine STI and HIV screening must be a part of our regular health
care regimen.
Sex while under the influence of any substance greatly increases
the chance of HIV transmission because a person's ability to negotiate
safer sex may be impaired. We must support efforts by men to minimize
or eliminate their use of alcohol and/or drugs especially before
and during sex. Treatment of addictions must be viewed as integral
to our STD and HIV prevention efforts.
Dialogue:
Dialogue is also critical during these times. Whether over a dinner
table with friends and family or in bed with a boyfriend or trick,
we must have the difficult conversations about why we should
matter to ourselves, each other and the world. Here are some
questions to get the discussion going:
- Why should gay men matter to each other?
- How do we extend consideration and concern to other men with
whom we have sex?
- How do we feel about our bodies as gay men and how do those
feelings influence the decisions we make about the sex we have
or the drugs we use?
- What motivates some gay men's abuse of crystal?
- Is self-policing a viable strategy for gay men?
- What will self-policing really mean inside of gay communities
that are already highly divided by race, class, and sero-status?
- How can we promote a progressive gay men's health agenda in
a socially and politically conservative environment?
- How can we respond to questions about complacency among gay
men?
- What are the long term psychological and social consequences
of prolonged periods of HIV vigilance?
- Where is the outrage over depictions of gay men as the embodiment
of terror as government officials and some elements of the mainstream
media continue to portray us, especially those of us living with
HIV as walking time bombs ready to explode HIV all over the concerned
public?
Action:
There has never been room for complacency or resignation in our
fight to end the HIV/AIDS epidemic. We must remain deliberate
in our organizing efforts. Here are some organizing principles
to be mindful about as we ready ourselves for the continued work
which lies ahead:
- Understand and reject HIV/AIDS stigma. Stigma can serve as
the basis for discrimination. Its sole function is to exclude.
Exclusion will not work as an STD/HIV prevention strategy.
- Insist that every sex act be an expression of consideration
as well as desire.
- Resist urges to police other men, but instead surprise your
friends, lovers, sex partners, family members, and acquaintances
with conversations about sex, love, crystal use, relationships,
homophobia, HIV/AIDS, racism, work, art, and the million other
things that matter to you.
- Request participatory, open-ended and community-level interventions
aimed at signaling to all gay men that we matter — to each
other and to the world. These can range from pot-luck dinners
to 12-step programs; from story-telling circles to interactive
internet-based programs; from personal art projects to large
scale home-grown social marketing campaigns; from reading groups
to community forums.
- Demand gay sensitive, culturally relevant mental health programs,
addiction services and treatment strategies for men who have
sex with men.
- Establish alliances that are unexpected and that break from
HIV/AIDS industry convention (civil rights groups, anti-hate
crime advocates, art organizations, anti-poverty coalitions,
etc.) as a strategy for addressing the contextual factors underlying
heightened risk for STD and HIV.
- Work to end homophobia, racism, sexism, HIV/AIDS stigma, transphobia,
and poverty as part of a broader health and wellness agenda for
men who have sex with men.
Sadly, there is no cure for AIDS. Nor is there a magic bullet
to prevent the transmission of HIV. If nothing else, the media
attention about multi-drug resistant HIV reminds us about the seriousness
of HIV/AIDS disease. We must move past the trivialization of HIV,
because living with AIDS is neither glamorous nor easy. Now more
than ever, we must re-affirm with dignity the many expressions
of love and pride we extend to ourselves and to each other. We
must continue to advocate for comprehensive and creative prevention
approaches that are multi-pronged and sustained over time. In the
current challenging political and fiscal environment, this will
require our collective, unrelenting, and steady resolve.
Men, Meth and Sex
By Bob Huff
The Journal of Urban Health recently released an advanced access
version of a special issue devoted to investigations of substance
use and sexual risk behavior among men who have sex with men (MSM).
Some of these papers may offer useful insights for designing interventions
and understanding the complex motivations that drives high risk behavior
and continuing HIV transmissions in what is often referred to as
a "community" but are, as is evident from these studies, highly diverse
populations of individuals with many differing motivations and behavior
patterns.
These brief reviews are based on abstracts published at jurban.oupjournals.org.
Heavier drug use associated with lack of impulse control;
unprotected sex.
Patterson and colleagues from San Diego classified a sample of
261 HIV-positive gay male methamphetamine users by their drug use
patterns: meth use only, 5%; light users (meth with marijuana or
poppers), 31%; and heavy users (meth with cocaine, heroin, ketamine,
etc.), 64%. Heavy drug users were younger than light drug users
(35.6 vs. 38.4 years) and had not used meth for as long as light
users (10.3 vs. 14.2 years). Both heavy and light users used meth
and alcohol in similar amounts and frequency. The heavy users reported
more unprotected sex with more partners of seronegative or unknown
status. Heavy drug users also had higher scores on tests of impulsivity
and negative self-perceptions than did light drug users. The authors
propose further research on behavioral interventions to "evaluate
whether methamphetamine use and sexual risk behavior can be reduced
by modifying impulsivity and negative self-perceptions."
Patterson TL et al. Methamphetamine-Using HIV-Positive Men
Who Have Sex with Men: Correlates of Polydrug Use
Discussion more inviting than counseling or drug treatment
In seeking to recruit drug-using gay men into a behavioral intervention
study, Kanouse and colleagues in Los Angeles found the men were
more willing to respond to advertisements for discussion groups
about drugs and sexual behavior than to advertisements for interventions.
Of those who participated in the discussion groups, 58% subsequently
volunteered for counseling although only about a third of those
accepted drug treatment. Men who accepted counseling reported
high levels of drug use and sexual activity. The authors recommend
a two-stage process of first recruiting into discussion groups
before offering behavioral interventions.
Kanouse DE et al. Recruiting Drug-Using Men Who Have Sex with
Men into Behavioral Interventions: A Two-Stage Approach
Participation in meth therapy study reduced depressive
symptoms Peck and colleagues from Los Angeles investigated
the association between meth use and depression in 162 gay male
participants in a 16-week randomized trial of four behavioral
interventions for meth use. Methamphetamine use was documented
by urinalysis and depression symptoms were self-reported.
At baseline, 73.2% had depressive symptoms rated mild or higher
with 28.5% rated moderate to severe. All participants reported
improved symptoms by end of study regardless of assigned intervention
and that depressive symptoms remained improved to one year after
study entry.
Peck JA et al. Sustained Reductions in Drug Use and Depression
Symptoms from Treatment for Drug Abuse in Methamphetamine-Dependent
Gay and Bisexual Men
Snapshot shows high prevalence of childhood sexual abuse
in men with associated depression and sexual risk taking
Holmes and colleagues from Philadelphia explored the factors of
childhood sexual abuse (CSA), post-traumatic stress disorder (PTSD)
and depression on sexual risk taking in a randomly selected telephone
survey of men from Philadelphia County 18–49 years of age.
Of 197 participants, 43 (22%) had histories of CSA, which was
significantly associated with PTSD and depression (p=0.3). These
factors were also associated with the number of lifetime sexual
partners.
Holmes WC et al. Men's Pathways to Risky Sexual Behavior:
Role of Co-Occurring Childhood Sexual Abuse, Posttraumatic Stress
Disorder, and Depression Histories.
Internet chatrooms effective for recruiting MSM with high
risk sexual and drug use behaviors
Fernández and colleagues from Miami report on the use of Internet
chat rooms to recruit Hispanic men who have sex with men (MSM)
into community-based HIV research studies. In 211 hours of chatting
over 2 months with 737 individuals, 176 participants were recruited
to visit community sites for screening and enrollment. Of 172 eligible
participants, 48.5% had used party drugs, including methamphetamine
(11.7%), cocaine (15.8%), ketamine (3.5%), poppers (31.6%), ecstasy
(14%), GHB (3.5%) or Viagra (19.3%) within the prior 6 months.
Drug use was significantly associated with higher numbers of sex
partners, higher social isolation scores and participation in unprotected
receptive anal intercourse.
Fernández MI et al. Surfing New Territory: Club-Drug
Use and Risky Sex Among Hispanic Men Who Have Sex with Men Recruited
on the Internet
Meth or Coke: differing motives for stimulant use by Latino
gay men
Diaz and colleagues from San Francisco reported on methamphetamine,
powder and crack cocaine use in a randomly selected sample of 300
Latino gay men who had used stimulants in the past six months.
Methamphetamine was the most frequently used stimulant (51%), followed
by cocaine (44%), and crack (5%). Overall, reported motives for
stimulant use included the desire for energy, sexual enhancement,
social connection, coping with stress, and work productivity, with
meth users stressing sexual motives (better sex, more sex, more
anal sex) and cocaine users stressing social motives (enhanced
sociability and to fit in with other gay men). According to the
authors: "Latino gay men were found to rely on methamphetamine
for reasons related to sexual enhancement, possibly to meet cultural
expectations and norms of sexual prowess and sexual success in
the gay community."
Díaz RM et al. Reasons for Stimulant Use Among Latino
Gay Men in San Francisco: A Comparison Between Methamphetamine
and Cocaine Users
Both light and heavy drug use associated with increased
sexual
risk taking
Colfax and colleagues from San Francisco tracked patterns of methamphetamine,
poppers, and cocaine use with sexual risk behavior in 736 gay men
over 48 months. Although use of meth, poppers and cocaine declined
among participants overall during the study period, younger individuals
were more likely to increase drug use over time. During periods
of drug use, high risk sexual behavior (unprotected anal receptive
sex with a partner of unknown serostatus) increased along with
the increasing frequency of drug use, compared to periods of no
drug use. The authors conclude: "These results suggest that even
intermittent, recreational use of these drugs may lead to high-risk
sexual behavior, and that, to reduce and prevent risks of HIV,
no level of use of these drugs should be considered 'safe.'"
Colfax G et al. High-Risk Sexual Behavior Among a Cohort of
San Francisco Men Who Have Sex with Men
Young HIV-negative drug-using MSM of color face higher
risks than older HIV-positive men.
Fuller and colleagues from New York recruited from the street a
sample of injecting and non-injecting heroin- and cocaine-using
MSM, aged 18 to 40. Of 95 MSM who used heroin or cocaine, 25.3%
were HIV-positive (75% previously diagnosed); 46% were black; 44%
Hispanic. The median age was 28 years with HIV-positive men more
likely to be older. However, HIV-positive men reported fewer high
risk characteristics (homelessness, illegal income, heterosexual
identity, multiple sex partners, female sex partners and sex for
money or drugs) than did HIV-negative men.
Fuller CM et al. A Comparison of HIV Seropositive and Seronegative
Young Adult Heroin- and Cocaine-Using Men Who Have Sex with Men
in New York City, 2000–2003
Risk behaviors in injecting MSM vary by self-identified
sexual orientation
Kral and colleagues from San Francisco collected data from 357
injection drug using MSM to analyze relationships between HIV serostatus,
risk behaviors, self-reported sexual orientation, and social service
utilization. Although 28% were HIV-positive, rates of risk behaviors
were similar within the cohort, with needle sharing reported by
30% of the HIV-positive group and by 40% of the HIV-negative group.
Similarly, anal intercourse within the prior six months was reported
by 70% and 66% of the HIV-positive and HIV-negative participants,
respectively. HIV infection was diagnosed in 46% of gay identified
participants compared to 24% of bisexual and 14% of heterosexual
identified MSM. The latter group was more likely to be homeless
or trade sex for money or drugs, least likely to have anal intercourse,
and about as likely as bisexuals to have sex with women. Bisexuals
were as likely as gay men to have anal sex. In this study, which
ended in 2002, 15% of HIV-positive participants were on antiretroviral
therapy, 18% were in drug treatment and 87% had used a syringe
exchange program within the past six months.
Kral AH et al. HIV Prevalence and Risk Behaviors Among Men
Who Have Sex with Men and Inject Drugs in San Francisco
Increased risk behavior and HIV prevalence in male sex
workers spanning sexual networks in multiple cities
Williams and colleagues in Houston interview 42 drug-using male
sex workers (MSW) during the period May 2003 to February 2004 to
determine patterns of travel and participating in sex work in other
cities. About half the participants reported traveling and working
in other cities, primarily in the Gulf Coast and Florida. A greater
proportion of MSW who traveled were self-identified as homosexual,
were HIV-positive, injected drugs more frequently and had significantly
more male sex partners than those who did not work different cities.
Williams ML et al. Spatial Bridging in a Network of Drug-Using
Male Sex Workers
Stigma renders black MSM invisible in the black community
Miller and colleagues in New York interviewed 21 black MSM in a
low-income, high HIV prevalence community in Brooklyn, New York.
Recent sex with a woman was reported by 71% of the men, with
43% self-identified as heterosexual and 24% as bisexual. Because
of adherence to masculine role expressions in the community reinforced
by stigma, male partners were typically identified through the
private sex clubs or on the Internet. The authors conclude: "A
focus on sexual orientation and bisexuality has obscured the
issue of race in the HIV/AIDS epidemic among Black MSM. In the
long term, public health promotion and HIV prevention will require
greater tolerance and acceptance of sexual diversity in the Black
community."
Miller M et al. Sexual Diversity Among Black Men Who Have
Sex with Men in an Inner-City Community
Feminization of AIDS: Ten
Unavoidable Choices for African Leaders
By Dr. Chinua Akukwe
The UNAIDS report on the HIV/AIDS pandemic highlights the growing
rates of infection among women worldwide. Women now account for
nearly 50% of all individuals living with HIV/AIDS worldwide. However,
in Africa, the situation is more ominous. Almost 57% of all individuals
living with HIV/AIDS in Africa are women. For Africans ages 15-24
living with HIV/AIDS, women account for 76% of all infections.
In South Africa, Zambia and Zimbabwe, young women ages 15-24 have
rates of infection that are between three and six times that of
their male peers. The so called feminization of AIDS appears to
be in full swing in Africa. The key question is whether African
leaders and elite are ready to make hard choices that would slow
down the rate of infection among women. I briefly review these
choices. The key is to focus on practical solutions to a problem
that can only get worse if nothing is done.
First, are African leaders and governments ready
to mount a comprehensive and sustained information, education and
communication campaign against risk-behaving practices of men that
put women at risk of HIV infection? I am not aware of any African
country that is currently implementing a sustained, nationwide
campaign against sugar daddies, the use of large sums of money
by male clients to encourage sex workers to engage in unprotected
sex, the rape of young girls by school teachers, the molestation
of young girls by family members and the molestation of street
children. African men who have disposable income are at the root
of sexual networking in various communities that spread HIV, according
to the UNAIDS.
Second, are African leaders and governments ready
to address cultural practices that may put women at disadvantage
in the fight against HIV/AIDS? These practices include lack of
proactive opportunities for women to discuss sexual mores and risks
with their husbands, cultural expectations of subservience in sexual
matters, the culture of wife inheritance after widowhood, and,
the lack of property rights for widows or single women even when
they have to take care of small children.
Third, are African leaders and governments ready
to invest for the long term on female education? According to latest
data from the World Bank, 45% of women ages 15 and above in Sub-Sahara
Africa are illiterate. While 94% of boys are enrolled in primary
schools only 81% of girls are in school. For starters, primary
and secondary school education should be free in Africa to allow
young people, including girls, have a head start in life. It is
also important for African women to have increased access to university
education, especially those from poor families. However, to ensure
quality education for African women, African governments and rich
nations such as the United States and other Western democracies
should provide increased, targeted development assistance for Africa.
Rich nations and multilateral institutions such as the World Bank
and the International Monetary Fund should provide comprehensive
debt relief for Africa with a major condition that significant
portions of the savings from debt relief should go toward social
welfare programs such as financing of education initiatives for
girls and young women.
Fourth, are African leaders and governments ready
to create enabling environments for empowering African women? Limited
economic choices and opportunities constrict the capacity of African
women to negotiate safer personal behaviors, including sexual relations.
Although African women are major sources of economic wealth in
many rural parts of Africa, these women have limited control over
their generated income due to cultural taboos and traditional practices.
African governments should end cultural practices that deny women
the right to benefit from their toil and labor. It is also important
for African governments to create micro-credit facilities for enterprising
rural women so that they could become stable, small- scale entrepreneurs
and accumulate disposable income. Women with disposable income
are likely to make better personal choices for themselves and their
children.
Fifth, can African leaders and governments create
political space for women? Unlike many official statistics that
cite token numbers of national ministers and top government officials
that are women, I believe that in order to fight AIDS, women must
be in decision making organs in local and state governments throughout
Africa, and also have leadership roles in key national government
institutions such as the ministries of finance, national planning
and justice. In addition, African women should be in decision making
positions in civil society, local chambers of commerce and local
youth organizations that directly interface with the grassroots.
It is important to state without equivocation that female representation
in national cabinets in Africa should go beyond the obligatory "Ministry
of Women or Gender Affairs."
Sixth, are African leaders and governments ready
to create necessary legal climate and framework that protects women
from discrimination and lack of due process? UNAIDS estimates that
more than half of African countries do not have laws against discrimination
of individuals living with HIV/AIDS. In Africa, according to the
UNAIDS, the fear of a HIV test by women, including pregnant mothers,
is the beginning of wisdom, since negative societal consequences
and uncertain future may lie ahead if they test positive. For women
living with HIV/AIDS, the prospect of dealing with family, community
and government indifference and sometimes hostility, can be insurmountable.
Legal reforms on rape, sexual molestations, domestic violence,
favors-for-forced sexual relations, property rights, and ownership
of business are crucial in the fight against feminization of HIV/AIDS.
Seventh, are African leaders and governments
ready to invest in public health services that are friendly and
accessible to women? National spending on public health services
is low in Africa, about US$30 per capita, according to the World
Bank. Women face formidable challenges in accessing public health
services for conditions such as sexually transmitted diseases and
tuberculosis that are important facilitators of HIV transmission.
Privacy and confidentiality is rare in African health institutions,
according to the UNAIDS. Societal stigma is common when women become
linked to sexual transmitted diseases. In addition, fear of violence
may keep women from utilizing HIV preventive services or even showing
up for AIDS clinical care, according to the UNAIDS. It is important
for the international community to support African nations that
seek to implement female friendly health systems and programs.
Eighth, are African leaders ready to position
gender issues as a major priority of international development
assistance? Declarations, statements and formal speeches about
gender issues must be coupled with specific policy and program
initiatives to end gender inequities in Africa. African leaders,
continent-wide institutions and the civil society should make gender
equity a cardinal feature of their relationship with bilateral
and multilateral agencies. There is a tendency to point to token
appointments of women to prominent positions as celebratory signs
of progress on gender issues in Africa. While this is important,
the focus should be on hundreds of millions of African women who
toil away anonymously, unsung and uncelebrated despite their significant
contributions to the economy of the continent. In particular, African
governments should make ending gender inequity a top priority of
their partnership with donor agencies. A good measure of serious
commitment is the proportion of resources requested by African
governments to deal with gender inequities in proposals sent to
donor agencies. National budgets should also reflect increased
resources devoted to ending gender inequities and creating income-
generating opportunities for women.
Ninth, can African leaders lead the fight against
sexual violence against women? Official, societal and personal
silence on sexual violence against women is deafening in many parts
of Africa. In particular, perpetrators target female teenagers
in some parts of Africa, thereby potentially setting off a chain
of events that may leave the young women not only emotionally scarred
for life but also the ever possible risk and danger of HIV/AIDS.
To end sexual violence, African governments would have to deny
perpetrators of sexual violence, political, economic, legal and
social sanctuary. Zero legal tolerance against sexual violence
should be enforced and perpetrators subjected to the long arm of
the law. Women should be encouraged to come forward with cases
of sexual violence and the society should treat them with compassion
while the legal system runs its course.
Tenth, African leaders and governments must win
the battle against widespread poverty in the continent. Poverty
is a major reason why individuals, including women, knowingly engage
in high risk behaviors that facilitate the spread of HIV. Feminization
of HIV/AIDS is closely intertwined with poverty and harsh living
conditions. African leaders and governments should create opportunities
for poor women to escape poverty through sustainable macroeconomic
policies that improve their vocational skills, provide access to
literacy programs, provide incentives for self employment and allow
them to accumulate capital and properties. Rich nations, including
the United States should work closely with Africa leaders in this
regard. Comprehensive debt relief, increased access to trade for
African farmers and businesses, and comprehensive micro-credit
programs are also critical policy issues that rich nations can
assist African nations as part of a comprehensive fight against
poverty.
Conclusion
Efforts to end the feminization of AIDS in Africa must be African-
based and African-implemented. For the African woman at the receiving
end of HIV/AIDS, the solution lies principally in changing societal
beliefs and practices within her family, community, country and
the continent. The solution to gender inequities lies in the
capacity of African governments to confront societal beliefs
and practices that wittingly or unwittingly put women at risk
of physical, emotional and mental harm. The HIV/AIDS epidemic
in Africa is exposing deadly consequences of gender inequities.
As the toll of HIV/AIDS mounts in Africa and the epidemic gradually
assumes a feminine connotation, every policy maker in Africa
should work toward the end of all practices that prevent African
women from becoming full partners in the titanic struggle ahead.
Any serious advocate for comprehensive AIDS remedial efforts
in Africa cannot afford to watch from the sidelines the increasing
feminization of AIDS in the continent.
Chinua Akukwe is a member of the Board of Directors of the
Constituency for Africa, Washington, DC and an adjunct professor
of public health at the George Washington University, Washington,
DC.
12th Retrovirus Conference
on the Web
By Bob Huff
The Conference on Retroviruses and Opportunistic Infections (CROI)
is the most important AIDS science meeting of the year. The conference
organizers run a tight ship with attendance limited to working
scientists and a sprinkling of community members involved with
treatment advocacy and education. It is not a trade show and there
are no pharmaceutical company pavilions, free pens or slick sales
pitches at CROI.
Yet as exclusive at CROI is, it is also the most accessible HIV
meeting of the year owing to a commitment to webcast nearly every
important session on the Internet. This year, over 32 hours of
plenary talks, symposiums and special sessions are available for
free viewing at www.retroconference.com.
The webcasts offer audio and synchronized slides for those with
slow Web connections and streaming video plus slides on speedier
hookups. If you want a glimpse into the state of the art of HIV
research, these webcasts let you see and hear the people and ideas
that represent the latest understanding on nearly every aspect
of the virus and the immune system. You may not understand everything
you hear, but if you are truly curious about what makes HIV tick,
then many of these sessions will be fascinating and informative.
Here are some highlights of CROI 2005 on the Web:
Daniel Douek: Making Sense of HIV Disease Pathogenesis
Friday, 9:00 am
Douek blows the lid of what we thought about early HIV disease
progression. A stunning picture of how HIV ravages lymphoid tissue
in the gut within days of a new infection.
Bernard M Branson: Symposium: Rolling Out Rapid HIV Tests
in the United States
Wednesday, 4:00 pm
There is growing pressure to change how HIV is diagnosed in the
U.S. Branson traces the long and winding path to rapid testing.
Kasia Malinowska-Sempruch: Symposium: The HIV/AIDS Epidemic
in Eastern Europe
Wednesday, 4:00 pm
Injection drug use is driving the explosive spread of HIV in Russia.
So why are inflexible national drug policies standing in the way
of arresting this epidemic? No science jargon here, just the hard
reality.
Grant Colfax: Symposium: The Epidemiology of Substance
Use and Sexual Risk Behavior among Men Who Have Sex with Men:
Implications for HIV Prevention Interventions
Wednesday, 4:00 pm
Substance use — including crystal meth — is a key factor
in the continuing transmission of HIV among gay men in the U.S.
But what interventions have been shown to decrease substance use
and cut the risk? Jargon free!
Bob Grant: Research Overview: Pre-Exposure Prophylaxis
(PrEP)
Friday, 12:15 pm
Since a protective vaccine may be years away, the idea of using
tenofovir (Viread) in people with high risk behaviors is being
studied. It worked in monkeys (for a while). It may be safe. But
can it put a dent in runaway infection rates in the developing
world?
James McIntyre: Plenary: Controversies in the Use of Nevirapine
for the Prevention of Mother-to-Child Transmission
Wednesday, 9:00 am
For an update on the never ending nevirapine story and current
controversies in preventing mother-to-child transmission of HIV,
this webcast is must viewing.
Julie Overbaugh: Plenary: The Biology of HIV-1 Transmission
and
Re-Infection
Thursday, 9:00 am
Some people still don't believe in "superinfection." That's the
medical term for acquiring a new HIV infection on top of an existing
HIV infection. But HIV superinfection is a real possibility and
may occur as frequently as first infections do. Barebackers take
note!
Special Symposium on the "Super Bug"
Thursday, 6:00 pm
A special session was called to address the press frenzy over an
announcement that a new, potentially virulent and drug-resistant
strain of HIV had been found. Overall, this was a remarkably dull
take on a hot topic, but these two presentations are worth a look: David
Ho: Case Report of Recent Infection by a Multi-Drug Resistant,
Dual-Tropic HIV-1 in Association with Rapid Progression to AIDS
Significant finding or headline-hogging scare tactic? David Ho
lays out the facts about the New Yorker with multi-drug-resistant
virus and a fast-moving case of AIDS.
Harold Jaffe: Public Health Aspects of the NYC Case
The former CDC head takes a common sense look at the real prevention
issues behind the hype.
These sessions might be tough going for the uninitiated, but it's
surprising how quickly one starts to pick up the key concepts after
hearing them a few times. Of course, plenty of people don't want
to hear about it, and that's fine too. Let's face it: there's no
red carpet or paparazzi at CROI — just several thousand very
smart people working hard to end this epidemic. Give them a play.
View
Webcasts
www.retroconference.org
CROI's webcast technology is easy to navigate. Select the
day and session you want to view and the program begins to
play in a separate window. Click on "Index" and you can jump
to the speaker or topic that interests you. On some browsers
you can even play the videos at a higher speed, which lets
you move through dull stuff at a faster pace. You can also
slow down the playback to take notes, which offers the added
amusement of making some of the world's most prominent scientists
sound like they are on quaaludes.
|
Basic Training
Reviewed by Bob Huff
CROI Webcast
Tuesday, 9:00 am
Workshop for New Investigators
This special session was organized for young scientists to entice
them into studying emerging research topics in the basic science
of HIV. It provides an overview of some of the key unanswered
questions about how HIV behaves in the body and how the body
behaves when infected with HIV. Nearly 25 years into the age
of AIDS, it is sobering to learn how much we don't know about
this virus.
Molecular Virology
Ned Landau
This lecture reviews the big three of the known interdependencies
between HIV and human host proteins. HIV carries a relatively small
toolkit of viral proteins which adapt and hijack human cellular
proteins in order to replicate. For example, there is a natural
anti-viral protein in cells called APOBEC 3G that would force HIV
to mutate into an increasingly mangled state if it were not deactivated
by a small viral protein called Vif. One potential therapeutic
strategy would be to defeat Vif and let APOBEC 3G take care of
the virus. Another natural chain of events that normally acts as
the "garbage collector" of the cell is somehow subverted by HIV
into chaperoning newly forming virus particles as they migrate
to the cell's surface to be released into the bloodstream. A therapy
that could disrupt this hijacked system would leave HIV harmlessly
trapped inside the cell. Then there is TRIM5-alpha, possibly another
natural antiviral factor found in monkeys and humans that is able
to stop HIV before it gets started in monkeys, but is only weakly
active in humans. Could a drug make man more like a monkey? There
are more of these virus/host interactions known (hRIP is one) and
likely many more yet to be discovered, but these three are keeping
scientists busy this year.
Viral Pathogenesis
John Coffin
This talk provides an overview of how HIV causes disease, how it
evades the immune system and why it is so hard to treat. HIV is
unique among viruses because it preferentially infects activated
memory CD4+ T cells, a type of cell that the body normally makes
in abundance in response to an immune challenge. Typically, when
the challenge has passed, the excess T cells cells are recycled
and the immune system quiets down. But in HIV infection, this episodic
response becomes a continuous state of alert, with billions of
CD4 cells becoming activated, infected, and destroyed in an ongoing
cycle. Activated CD4 cells typically live for only about a day,
but before they go, these doomed cells make enough new virus to
infect an equal number of newcomers, thus holding the total number
of infected cells — and the amount of virus they produce — relatively
steady from day to day. But over time — ten years on average,
but in as little as a few months or as long as never — this
balance between the creation and destruction of CD4 cells slips
toward depletion, resulting in a dangerous loss of immunity. Although
there are many theories, we still don't know exactly how the steady
state of chronic HIV infection turns into AIDS.
When a person with measurable viral load begins taking an effective
antiretroviral drug, their viral load can drop until it almost
seems to disappear. Although the standard for successful viral
suppression is "undetectable" virus of less than 50 copes per mL
of blood plasma, more sensitive tests can usually find at least
2 or 3 copies of HIV still hanging around. One theory is that these
stragglers may be coming from long-lived memory cells that have
been quietly warehousing HIV and only occasionally become activated
to produce new virus. Yet these few cells are enough to spark a
return to full-scale replication if drug therapy is removed or
stops working. One reason therapy might stop working is if a random
mutation allows a single virus to resume replicating despite the
drugs. The persistence of archived virus is also why complete eradication
of HIV is considered so unlikely.
This leaves us with a few big questions: How does HIV kill infected
cells? How does HIV cause AIDS? Where in the body does HIV replicate?
What is the source of that low-level persistent virus?
If you think these seem like basic questions, you are right. While
there are many theories, science is still wrestling with some very
fundamental problems about what HIV is doing in the body. Hopefully,
a new crop of young scientists will be motivated to help find these
answers.
Immunopathogenesis
Rick Koup
One of the most vexing unanswered questions in AIDS is: How does
HIV escape control by the immune system? In most newly infected
people, the immune system is able to provide some initial defense
against HIV, but all too soon the virus begins to mutate and is
soon able to escape suppression. The CD8+ T cells have much of
the responsibility for recognizing and eliminating HIV, but they
are never quite able to keep up with the shifty virus. There is
also some evidence that HIV actually helps defeat the defenses
by altering the way these immune cells work. CD8+ T cells in people
with HIV often contain a different mix of signaling and cell-killing
substances than in people without HIV. So, is this a result of
the cells adapting to control HIV or is HIV itself causing these
cells to change? Another big question: does chronic immune activation
lead to increased HIV replication or does increased replication
lead to immune activation? Understanding these issues will be critical
to the development of a vaccine or an immune-based therapy for
HIV.
HIV Vaccines and Neutralizing Antibodies
Dennis Burton
If cellular immunity is impaired by HIV, what about the other main
arm of the immune system, antibodies? Most researchers think that
any successful vaccine to prevent infections in a new host will
need to stimulate antibodies capable of neutralizing transmitted
HIV. But HIV is changeable and well-protected. Several promising
antibodies have been found, but the problem is they either don't
recognize a wide enough range of HIV variants or if they do, they
are too weak to neutralize the virus. The dual problems of HIV's
escape from antibody-based immunity and CD8+ cell-based immunity
are why few foresee an effective vaccine within the next ten years.
That's one reason why, with so little success in effecting immune
control of the virus, the attention of this conference inevitably
turns to drugs.
Plotting the Perfect Protease
Inhibitor
Reviewed by Bob Huff
CROI Webcast
Symposium: Antiviral Drug Discovery
Dale Kempf. HIV Protease: Can Better Inhibitors be
Found? Thursday, 4:00 pm
Protease inhibitors (PIs) are potent anti-HIV drugs — their
arrival in 1995 was the main reason that AIDS death rates plummeted
soon after. But PIs have their problems. If they don't send you
running to the bathroom, they can cause one of your blood test
values to soar or your kidneys to ache. Dale Kempf, of Abbott Laboratories,
and one of the architects of Kaletra, discussed some new tools
drug developers are now using to screen out these unwanted side
effects before a new PI candidate ever gets into a human body.
The most obvious quality for any ideal HIV drug is potency. It
should be able to quickly knock down viral load levels to the point
where the virus is just barely replicating. Ideally, the drug should
be able to do this not only for the virus that is most commonly
found in the community (wild-type) but also for HIV that has become
resistant to all other available drugs. And it should continue
working even if a few new resistance mutations happen to crop up.
These are all aspects that can be tested in the laboratory, and
these are the qualities that drug designers look for first. In
the old days, that was enough. But problems with existing PIs — namely
their side effects and their propensity to interact with the blood
levels of other drugs — keep us searching for the perfect
PI.
The most attractive feature of the protease inhibitor Reyataz
is that it doesn't cause the elevated blood lipid levels (cholesterol
and triglycerides) that can come from using Kaletra. Unfortunately,
this newer PI has its own quirky side effect that can make the
eyeballs of some of its users turn yellow due to excess bilirubin
in the blood. Kempf reports that scientists have been using new
lab-based tools to understand the underlying mechanisms of these
side effects so they can be avoided in future drugs.
New technology allows a drug to be tested against an array of
tens of thousands of human genes all at once. Genes that become
activated when exposed to the drug are targeted for further investigation.
This was how Abbott scientists learned that Norvir, but not Reyataz,
inhibits a cellular recycling system called the proteosome,
which had been implicated in the lipid problem. Knowing this, Kempf
and colleagues began looking for a potent PI molecule that didn't
affect these proteosome genes. After several tries they found a
promising candidate and continued tweaking it until it passed a
similar test that looked for effects on bilirubin production. This
finalist candidate was called A-792611 (at this early stage drugs
have only numbers, not names) and it looked promising, with ten
times the potency of lopinavir (the active PI in Kaletra) and little
likelihood of sharing either Kaletra's or Reyataz's side effects.
At this point the drug scientists began assessing the potential
for "611" (the compound's nick-number) to interact with other drugs.
PIs are notorious for speeding up or slowing down each other's
metabolism. While Norvir was originally developed as an antiviral
drug, its true talent is in slowing down the elimination of other
PIs. This "boosting" effect keeps PI blood concentrations higher,
longer, which has made protease inhibitor therapy much more convenient
and reliable than when it was first introduced. While "611" did
not speed up the removal of other drugs, it stumbled when the assay
revealed that it shuts down a key avenue of drug metabolism. Since
this would have caused extreme and unmanageable drug interactions
in real life, that was the end of the line for "611". Fortunately,
all of this was discovered quickly and efficiently, and the molecular
fiddling goes on to find the ideal PI candidate to take forward
into human testing. Of course, surprises will always arise once
a drug starts being used in people, but these new preclinical checkpoints
should help increase the chances that the next PI down the pike
is as easy on your body as it is tough on HIV.
Supertramp:
What Ever Happened to the Sex Radicals?
By Daniel Raymond
It's official: Superbug fatigue has set in. Nobody held a press
conference, but the case report that launched a thousand news articles,
watercooler conversations, and heated e-mail exchanges has passed
from the acute phase into the chronic fate of overhyped AIDS stories:
after a shiver of anxiety, a collective shrug of indifference.
Intensive media coverage failed to ignite mass hysteria; gut reactions
seemed to run a short gamut from "So what else is new?" to "This
just proves what I've been saying all along!" But the fact that
everyone was talking suggested that this "superbug," whatever its
merits as a clinical phenomenon, clearly represented a potent meme,
or unit of cultural information. Memes are to culture what genes
are to biology.
The superbug meme adapted itself to a remarkably broad range of
hosts — it evolved into strains tailored to support virtually
everyone's agendas. We saw public-health officials fretting and
prominent researchers bickering over the significance of the case,
while press releases from the HIV/AIDS community provided healthy
doses of skepticism and context embedded in well-rehearsed calls
for more funding and better prevention policy, while conservative
commentators drafted Patient X into their war on hedonism and moral
decay.
But the novelty of the superbug meme quickly dissolved into a
mix of now-familiar cultural struggles around promiscuous gay sex
and illicit drugs. The superbug may not be spreading, but it briefly
illuminated a landscape of out-of-bounds bodies and the pleasures
they seek.
The persistent cultural fascination with a rampant, renegade version
of gay male sexuality may seem anachronistic after a domesticated
decade of Will & Grace and gay marriage debates. Political pressure
forced a retreat from creative HIV prevention campaigns and threatens
to stifle research into the highways and byways of sex on the margins
of society. Even current discussions of the prevention of sexual
transmission of HIV between men (under the anodyne acronym MSM)
increasingly seem to focus on tepid, unsexy themes like self-esteem
and responsibility.
But the last several years also generated a steady diet of new
incarnations of the sexual outlaw at regular one to two year intervals:
barebacking, "bug chasers" and "gift givers," surging syphilis
rates and internet-enabled anonymous sex, men "on the down low," and
crystal meth-fueled sex fiends, to name a few.
The current focus on crystal meth brings a new twist, linking
sexual deviance to a long-standing tradition of moral panic around
drugs. From a harm reduction perspective, the recent anticrystal
campaigns are a familiar remix of reefer madness and "just say
no" style demonizations of a drug and, by extension, the people
who use it. The relentless coupling of crystal meth and HIV in
some "educational" materials would lead one to think that on crystal,
unsafe sex and resultant HIV infection are all but inevitable.
I've taken to joking that I want to start a counteradvocacy group
of people who've used crystal and never got HIV. Not a pro-crystal
group, per se, but a pro-reality group, to break through misleading
and ultimately counterproductive rhetoric.
At the height of the AIDS epidemic in the United States, some
people were committed to telling the truth about sexuality to power — and
each other. I still remember the sense of liberation in the early
'90s from reading certain 'zines — Scott O'Hara's sexy yet
matter-of-fact "How I Got AIDS: Memoirs of a Working Boy," serialized
in Diseased Pariah News, or Pat Califia's essay in Frighten the
Horses about the struggles and contradictions of safer sex, and
how and why we slip. These sex radicals pushed buttons and boundaries,
all while maintaining a politically engaged commitment to exploring
and documenting the messy, murky, contradictory truths of desire.
Radical AIDS activism and queer cultural politics blended and fed
each other in new fusions and recombinations resembling nothing
so much as sex itself.
We need that energy now — the response of the HIV community
to the superbug Sargasso betrayed a bankruptcy of new ideas, new
strategies, new narratives. Nobody even attempted to defend Patient
X, much less understand or identify with him. Advocates used the
case to press for more prevention dollars, without any explanation
of how current programs could have prevented this infection if
adequately resourced and freed from political constraints. HIV
prevention is in a silent state of crisis — we're not doing
any better now, and we've ceded our power and knowledge to the
CDC, just as communities — or, more accurately, social networks
and subcultures — have conceded the responsibility for prevention
to AIDS service organizations.
Perhaps we could start by breaking down the boundaries between
people who work on preventing sexual transmission and people who
work on preventing transmission in injection drug users (IDUs).
It's increasingly clear that alcohol and drugs play a role in a
lot of HIV infections through sex and that a lot of IDUs actually
get HIV from sex rather than needles. Both camps have different
conversations, different agendas, and different struggles. But
maybe that provides fertile ground for the kinds of fusions and
recombinations that could reignite HIV prevention as a movement,
not just an institution.
Daniel Raymond is the hepatitis C policy analyst for the Harm
Reduction Coalition.
© 2005 Gay Men's Health Crisis
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