UK Community Advisory Board (UK-CAB)

UK-CAB 13 – Introduction to immunology – entry inhibitors

3 June 2005

Reading material Part one
Reading material Part two


08:45–09:15 Registration and coffee/tea
09:15–09:30 Introductions, outline for the day
09:30–11:00 Entry inhibitors – part 1 – Gus CairnsOverview of the way entry inhibitors work including:

  • mechanisms of action – differences between CCR5 and CXCR4 inhibitor
  • current drugs in pipeline
  • potential advantages and disadvantages
  • issue of wide range or activity in different individuals
  • sensitivity of R5/X4 tests
11:00–11:30 Break
11:30–12:15 Entry inhibitors – part 2 – Simon Collins

  • issues with current studies
  • trial ethics for new drugs – background to European
    and US activist discussions
  • trial design for naive and experienced people
12.15–13.00 Conference feedbacks – all

  • Retrovirus
  • South African PWA conference


Introduction to immunology – Gareth HardyGareths response to his HIV-diagnosis was to go back to college to study biology A-level and learn as much as he could about immunology. He was a community activist in the 1990s including writing articles for some of the earliest issues of Positive Nation.For his PhD, Gareth designed and ran the Remune + IL-2 + HAART study at the Chelsea and Westminster hospital, and he has presented results from this and other studies at many of the larger international HIV conferences.This introduction to immunology with cover differences between cellular and humoral immune responses (that we first covered in the vaccine CAB), and other different ways that the immune system works including function of naive cells and the thymus, and response to successful HAART.

There will also be time for discussion on future research plus any other questions relating to this important subject.

15:30–16:00 Internal discussions – any other business
16:00 Meeting close

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Reading material (part one)

The first linked article is very short. This text summary for the next two articles is much clearer with the pictures, but I’ve pasted the text below. If you can use the links to see the web-based original material it is much easier to understand than the text file attached here and pasted below.

Gareth Hardy will be able to answer any questions you have about the reading – and any questions about HIV-related immunology. Any reading you can do before the meeting will make the discussion and training much easier to understand.

This short glossary may help:

The Immune System – Cells in our bone marrow, thymus, and the lymphatic system of ducts and nodes, spleen, and blood that function to protect us.

Antigen – Anything causing an immune response, usually foreign material but may be our own tissues.

Pathogen – Any disease causing micro-organism.

Tolerance – Non-reactivity of the immune system, usually refers to “self” but may include foreign tissue in organ transplants.

Autoimmunity – A failure of tolerance, the immune system reacts to self.

Chemokines – Molecules released by pathogens and infected tissues to attract cells of the immune system.

Cytokines – Signaling molecules released by one cell to cause a response in another. Signaling is extremely important in our immune response.

Innate immunity – Protection that is always present. Includes phagocytic (cells that eat other cells) macrophages and dendritic cells.

Adaptive immunity – Protection that arises by an immune response, including humoral immunity producing antibodies and cellular immunity.

Introduction to immunology:

Immune response: overview:

Immune response to HIV:

If you want more detail on any aspects of immunology, then the links form the introduction page have more detail on the following areas:

1. Pathogens and antigens
2. Cord blood transplants
3. Innate immune response
4. Adaptive immune response
5. Antibody diversity
6. Antigen combining sites
7. Allergy
8. Cellular immunity
9. Clonal selection theory
10. Regulation by the MHC
11. Lack of immune response to self
12. HLA genetic diversity
13. Monoclonal antibodies

Introduction to Immunology

History of Vaccinations


The Chinese are credited with making the observation that deliberately infecting people with mild forms of smallpox could prevent infection with more deadly forms and provide life long protection. Knowledge of the technique, known as variolation, worked its way west to Turkey by the 18th century.

Lady Mary Wortley Montagu, the wife of the British Ambassador to Turkey and who had once survived smallpox, had her children treated and brought the ideas back to Britain, where research began on how to reduce the inoculation’s sometimes-awful side effects.

In 1798, the British physician Edward Jenner published his long-term observation that cowpox exposure protected milkmaids from smallpox. To see if this protection could be artificially induced, he exposed a “healthy boy” to cowpox virus from a milkmaid, and then attempted to infect the boy with smallpox. (Obviously, this experimental method is unethical by today’s standards.) This method works because cowpox shares antigens with smallpox, but doesn’t cause the disease.

Fortunately, the vaccine worked. The boy had developed an immunity to smallpox from his exposure to cowpox. The technique of vaccination against smallpox quickly spread through the world. In 1980, the World Health Assembly officially declared “the world and its peoples” free from endemic smallpox. The Immunization Action Coalition is an excellent source of information about childhood, adolescent and adult immunizations and hepatitis B educational materials.

Since the days of Jenner, scientists have made great progress in developing vaccinations for many diseases. The table to the left shows the effectiveness of three vaccines: measles, diptheria, and mumps.

Discrimination of self from nonself

The success of the immune system depends on its ability to discriminate between foreign (nonself) and host (self) cells.

Survival requires both the ability to mount a destructive immune response against nonself and the inability to mount a destructive response against self.

-David Huston, Biology of the Immune System, JAMA 278 (22)

When an organism is threatened by microorganisms, viruses, or cancer cells, the immune response acts to provide protection.

Normally, the immune system does not mount a response against self. This lack of an immune response is called tolerance.

In some cases, the immune system does mount an immune response against self. If an error is made, and an immune response is made against self, tolerance to self is lost. This condition is called autoimmunity (from Greek, “self-immunity”). Examples of autoimmune diseases in humans are: asthma, lupus, and arthritis.

The nude mouse cannot mount an immune response

The nude mouse has a defect in its immune system, and can only live if protected from pathogens. The mouse to the right has a transplant of rabbit skin, and can’t reject the foreign tissue. Mice with immune deficiencies are very useful in cancer research because human cancer cells can grow into tumors allowing new ways to test cancer therapy.

Important definitions

This problem set will make use of these terms, and give examples of their significance.

Immune Response – Overview

Innate immune response

The immune system protects the body from invading disease-causing organisms, or pathogens. Pathogens and other non-self molecules are antigens – foreign molecules recognized by the immune system, stimulating an immune response.

Innate defenses act immediately or within hours of a pathogen’s appearance in the body. Innate defenses are nonspecific – they target any pathogen. Innate defenses include:

  • Skin, which excludes most pathogens from entering the body.
  • Cilia in mucous membranes, which sweep out airborne pathogens and dust.
  • Tears, nasal secretions and saliva, which contain bacteria-destroying enzymes.

When these generalized defenses are breached, phagocytes (“phago-“=eating, “cyte”=cell) can migrate to affected areas and engulf pathogens. Granulocytes and macrophages are phagocytic white blood cells. This migration of white blood cells causes the redness and inflammation associated with infection. Some cells of innate immunity are of special importance for regulating our immune response. These cells called dendritic cells or Langerhans cells can move through out our body, and are particularly rich in our skin and mucus membranes of our body that are exposed to foreign material, including our disgestive systems, airways, and sexual apparatuses. When dendritic cells encounter foreign material, they also are phagocytic (eat the material), but have special receptors that allow them to distinguish harmless and pathogenic (disease causing) organisms. However, these cells carry fragments of pathogen to lymph nodes where they either prevent or stimulate an adaptive immune response. The decision about which response to cause depends on the foreign material (dangerous pathogens cause a dramatic response) and whether cells of your own body are sending out “danger” or distress signals. The significance of the dendritic cells is that they can prevent you from reacting against your own tissues, against food that you ingest or harmless materials from your environment, or they can tell the rest of your immune system to make an adaptive immune response.

Adaptive immune response

If innate immune cells (dendritic cells) decide that the material is dangerous (part of a virus or bacteria), then they stimulate a specialized group of white blood cells causes CD4+ helper T cells to become activated. CD4+ refers to a surface protein on this class of T cells. Helper T cells can stimulate another group of white blood cells called B cells to produce antibodies that bind that specific antigen and immobilize it, preventing it from causing infection. Antibodies are specific for only one antigen. B cells must interact with Helper T cells, other specialized white blood cells, to initiate antibody production.

Pathogens (viruses or bacteria) that escape antibody detection can enter and infect cells. The surface of infected cells changes, and this change is recognized by T cells. Cytotoxic T cells kill infected cells, preventing these cells from producing more pathogen. Cytotoxic T cells must interact with Helper T cells to regulate destruction of infected cells. Remember that the dendritic cells must activate CD4+ helper T cells before our bodies can produce B cells secreting pathogen specific antibodies or cytotoxic T cells to destroy infected cells.)

Human Immunodeficiency Virus (HIV) specifically attacks Helper T cells. Without an adequate supply of Helper T cells, the immune system cannot signal B cells to produce antibodies or Cytotoxic T cells to kill infected cells. When HIV has critically depleted the Helper T cell population, the body can no longer launch a specific immune response and becomes susceptible to many opportunistic infections. This immunodeficiency is described in the name acquired immunodeficiency syndrome, or AIDS.

Immunology and HIV: Immune system’s response to HIV

HIV is stopped by innate defenses. HIV cannot penetrate unbroken skin. HIV is transmitted through direct exchange of body fluids. Sexual intercourse is the most common mode of transmission. Blood to blood contact, such as through sharing needles for intravenous injection or blood transfusion can also transmit HIV. Infected mothers can pass HIV to their infants during pregnancy, birth and breastfeeding.

Additional information about HIV transmission

HIV transmitted through sexual activity enters the bloodstream via mucous membranes lining the vagina, rectum and mouth. Macrophages and dendritic cells on the surface of mucous membranes bind virus and shuttle it into the lymph nodes, which contain high concentrations of Helper T cells (CD4+ T cells).

Once HIV has entered the body, the immune system initiates anti-HIV antibody and cytotoxic T cell production. However, it can take one to six months for an individual exposed to HIV to produce measurable quantities of antibody.

HIV mediated disease

HIV enters the body and binds to dendritic cells (orange cells with projections) which carry the virus to CD4+ T cells in lymphoid tissue establishing the infection. Virus replication accelerates producing massive viremia and wide dissemination of virus throughout the body’s lymphoid tissues. An immune response againse virus causes some protection but a chronic persistant infection is established. The production of cytokines and cell devisions that regulate the immune response for protection also cause HIV replication. There is a rapid turnover of CD4+ T cells that ultimately leads to their destruction and to a change in lymphoid tissues that prevent immune responses. The figure is taken from Nature Medicine 9, 839 (2003) and is reproduced with permission.

Infected cells produce massive amounts of virus

Cellular immune responses to HIV

  • Cytotoxic lymphocyte production follows the rise of HIV in the blood.
  • HIV specific CD4+ T cells may be especially susceptible to attack and destruction by HIV. HIV binds to CD-SIGN, a glycoporotein expressed on dendritic cells. Migration of HIV bearing activated dendritic cells to helper T cell areas of lymph nodes may specifically infect helper T cells specific for HIV peptides.
  • Reductions in HIV specific helper T cell numbers may lead to decreased activation and survival of cytotoxic CD8 T cells.
  • Reduced CD4 T cells may also result in an incomplete activation of CD8 T cells that can remove HIV infected cells, resulting in a decreased ability to destroy virally infected cells.
  • High mutation rates of HIV also allow virus to escape adaptive immune responses.

Why are CD4 T cells depleted in HIV disease?

  • HIV infection induces both quantitative and qualitative defects in the CD4 T cell compartment.
  • HIV innoculated into the body is carried into draining lymph nodes by dendritic cells, resulting in the activation and infection of T cells that can be destroyed both by virus and cytotoxic T cells.
  • The process of activation may cause T cells that are not specific for HIV to become activated and undergo apoptosis. The observation is that many non-infected T cells die in HIV infected individuals
  • Peripheral lymphoid depletion is met by increased production of T cells from stem cells in the bone marrow. This process produces more actively dividing T cells which can be infected by HIV.
  • Overtime, the ability of the bone marrow to maintain increased T cell production is eroded, while mutations in virus result in the production of highly cytopathic variants that can escape immune destruction.
  • Impaired production results in the eventual collapse of the immune system.

All contents copyright © 2000-02. All rights reserved.
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Reading material (part two)

From HTB – Oct/Nov 2004

The X4 files: sampling the science on HIV co-receptors in Bangkok

Bob Huff, for GMHC

It has become conventional wisdom that the International AIDS Conference (IAC) is no longer the place to find cutting-edge research on HIV science. And although Track A, the basic science track at the conference, had fewer posters and presentations than the tracks for clinical research, prevention, social issues and policy, a respectable 618 basic science presentations were submitted and 439 accepted to the 2004 IAC in Bangkok. Here’s a selection of abstracts covering one aspect of HIV basic research of emerging importance.

As most people who follow HIV therapies have learned by now, HIV infects a new target cell through the process of entry, which can be described as having three basic stages. First, a protein on the surface of HIV attaches to a CD4 protein on the surface of a target cell. This step, attachment, allows the viral protein to change its shape so that it can bind with a different kind of protein on the cell’s surface, called a co-receptor. Then, after co-receptor binding and a few more intermediate steps have been accomplished, the virus can finally pull itself into contact with the cell’s surface, where the two merge in a process called fusion. After fusion is complete, the viral payload can be delivered and the process of hijacking the cell and turning it into an HIV factory is well on the way.

Fuzeon, the only approved entry inhibitor, acts to block the fusion process at the point when the virus is pulled into contact with the cell. As for the other steps, several experimental drugs are in development to block attachment and co-receptor binding. As a number of orally available entry inhibitor candidates move through the drug development pipeline (injectable Fuzeon was approved in 2003), concerns are being raised about a subset of the class, known as CCR5 blockers. Because there are two basic types of cellular co-receptors that HIV can use, drugs are being developed that block both kinds. The most common co-receptor protein that HIV uses for entry is called CCR5 or R5, for short. In someone who is newly infected, R5 is often the only kind of virus that can be found. But in about half of the people who develop advanced HIV disease, the virus begins to use another co-receptor called CXCR4, or X4. The shift to using X4 is considered a bad sign because it is often accompanied by a dramatic increase in the rate of T-cell depletion. It is not entirely clear if HIV with the X4 phenotype causes accelerated T-cell loss or if it is only a symptom of some other shift in the T-cell ecology, but everyone agrees: you want to avoid developing an X4-using virus.

This means there is a critical open question about using the new R5 blocking drugs: will they cause HIV to start using X4? And will that be worse than letting the R5-using virus chug along at its own, slower, but no less dangerous pace? So far there’s no solid evidence that blocking R5 will lead to HIV mutations that prefer using X4. But there is increasing evidence that some people may have small amounts of X4 virus in their bodies that could be given a green light to take over if their R5-using cousins are shut down. Again, it’s not clear if these were acquired at the time of infection or if HIV can mutate step-by-step from exclusively using R5, to using both R5/X4, to using only X4. While there is now an experimental phenotype assay that can detect R5, X4 and dual R5/X4-using virus in a person’s blood, it may not be sensitive enough in all cases to identify X4-using variants that are hiding in tissues or are only present in very small numbers. Now, as several pharmaceutical companies are getting ready to start large phase III trials for their R5 blocking drugs, discussion of the X4 problem is heating up.

One attractive feature of blocking CCR5 is that there may be little or no toxicity penalty to pay, since some people are born without CCR5 proteins on their cells and seem to suffer no ill effects. (Yes, it is rare for these people to become HIV infected, and when they do – via other co-receptors, no doubt – they tend to have a very slow course of progression.) But blocking CXCR4 may not be as trouble-free, since a lack of the protein has been shown to lethally prevent infant mice from developing normally. Nevertheless, a couple of X4-blockers have been used in human safety studies with no disastrous results. Ideally, it seems, one would want to use an X4-blocker in tandem with an R5-blocker to prevent the possibility of an X4-using HIV variant escaping and causing accelerated immune damage. But, in the first few upcoming trials, at least, the R5 blockers may have to work without a safety net as researchers rely on the imperfect assay to screen out those at risk for switching to an X4-using virus. If all goes according to schedule and no unforeseen problems with toxicity arise (and there is no guarantee that they won’t), the first oral entry inhibitors could possibly appear in expanded access studies by late 2006 and be approved for sale in 2007.

Here’s a look at some of what we learned about the R5 and X4 co-receptors at the International AIDS Conference in Bangkok.

It is recognised that HIV with the X4 phenotype is rarely, if ever, transmitted – even when the donor predominantly carries X4 virus. In sexually transmitted infections, it is thought, dendritic cells (DC) patrolling the body’s mucosal frontier are the first immune cells to contact HIV. However, instead of infecting the DC, HIV is internalised into a bubble-like vesicle and eventually carried to a lymph node, where it is introduced to circulating T-cells, normally the next line of defence in the immune response to foreign viruses. Unfortunately, these T-cells are the very cells that HIV prefers to infect. This is where HIV actually takes root in a new host.

So, why do R5 viruses seem to be favoured for starting new infections? In a laboratory-based study by J. Alcami and colleagues in Madrid, infections of T-cells by X4-using HIV were observed to be greatly reduced in the presence of dendritic cells, while infections by R5 strains were enhanced. This, the authors say, suggests that dendritic cells may produce a chemokine, or signaling factor, that effectively prevents X4 HIV from establishing a new infection – while having the opposite effect on R5 virus. In other words, if dendritic cells are the gatekeepers to HIV infection, they may routinely filter out X4 virus, which allows R5 viruses to initially become the dominant strain. [1]

Epi snaps

Although most people’s HIV infections start out using the R5 co-receptor, in about half the X4 strain will eventually appear at some point during their lives. But how quickly does this happen, and to whom? In Bangkok, two studies presented retrospective analyses of co-receptor usage in a large number of samples and correlated the R5 phenotype with viral load, CD4 count and other variables. A study by Harrigan retroactively evaluated samples and records from 806 participants in a cohort of treatment naive-adults in British Columbia, and a study by Moyle evaluated data and co-receptor phenotype in a collection of 169 stored samples from treatment-naive individuals. In general, both studies confirm that, within a given sample population, as the duration of HIV infection increases and CD4 counts decline, the prevalence of the exclusive R5 phenotype decreases and X4 and dual R5/X4 phenotypes become more common.

In the Harrigan cohort, detection of the R5/X4 or X4 phenotype increased from 6% in people with CD4 counts above 500 cells/mm3 to over 50% in those with CD4 counts below 25 cells/mm3. There was only one exclusively X4 phenotype sample in the cohort. The odds of having an X4-using virus increased by about 1.5-fold in those with CD4 counts between 200 and 500 compared to those above 500 cells/mm3; the odds were 5- to 7-fold greater in those with CD4 counts between 25 and 200 cells/mm3; and jumped to 17-fold greater in those with fewer than 25 CD4 cells/mm3. [2]

In the Moyle study, detection of the R5/X4 phenotype ranged from about 7% in samples with CD4 counts above 300 cells/mm3 to 46% in those with CD4 counts below 100 cells/mm3. There were no exclusively X4 phenotype samples. The mean CD4 count for the R5 samples was 307 versus 117 cells/mm3 for the R5/X4 samples. [3]

In neither study was viral load a significant predictor of co-receptor usage phenotype. In the Harrigan cohort, injection drug use was not correlated with having R5 or X4 HIV; in the Moyle study there was no difference between B and non-B HIV subtypes.

Crowd control

A study by Ito and colleagues of the National Institutes of Health in Bethesda, Maryland, investigated how competing “swarms” of HIV with different co-receptor usage phenotypes might interact within lymphoid tissue. They found that X4-using HIV variants – including R5/X4-using strains – were able to suppress replication of their R5-using competitors. Meanwhile, the R5 viruses had no effect on the X4 interlopers. The researchers identified several chemokines stimulated by X4 HIV that seemed to be responsible for suppressing the R5 variants. When a cocktail of these chemokines was added to lymphoid tissue with only R5-using HIV present, the same suppressive effects were observed. The authors suggest that a better understanding of these chemokine-induced effects could possibly lead to the development of a new approach to anti-HIV therapy. [4]

Max factor

Early in the history of the epidemic one of the first distinguishing phenotypes of HIV described by scientists was the ability of some strains to cause groups of infected cells to fuse into clumps called syncytia. Syncytium inducing (SI) HIV was recognised as a highly virulent form and it became associated with rapid progression to terminal AIDS. At one point it was thought that syncytium formation was HIV’s main mechanism for killing T-cells; to this day it is not entirely clear what is responsible for T-cell death in AIDS and multiple effects are suspected, ranging from apoptosis (cell suicide), to immune exhaustion through overstimulation to direct killing. Eventually, SI and non-syncytium-inducing (NSI) HIV were correlated with the X4- and R5-using phenotypes and the SI and NSI nomenclature was generally put on the shelf.

Researchers from the lab of Jay Levy in San Francisco investigated the patterns of gene expression in T-cells stimulated by infection with two different phenotypes of HIV, the old-school SI and NSI variants. The quantities of various RNA gene products from the test cells were analysed using microarrays that can detect thousands of known gene products to see which were upregulated and which were downregulated when compared to uninfected cells. They found that SI HIV tends to upregulate genes involved with production of a cellular factor called tumor necrosis factor (TNF), which is associated with immune hyperstimulation, a state often implicated in T-cell depletion. [5]

The observation that people with AIDS have high levels of TNF in the blood was also made very early in the epidemic. At Bangkok, a group led by A. Valentin of the National Cancer Institute in Maryland reported on their recent studies of TNF levels in 63 patients (30 controls) and the impact that TNF has on virus production and co-receptor availability. They found that TNF inhibited replication of R5-using HIV strains while having no effect on X4 HIV. TNF was also observed to downregulate the number of CCR5 co-receptors that appear on the surface of T-cells, which could explain why R5-using viruses have such a hard time of it when TNF levels are increased. [6]

Couple this with Bonneau’s finding that X4 HIV stimulates TNF production, and you have one possible explanation for how the shift from R5 to X4 predominance occurs. Of course, these shifts may be happening all the time on a small scale in isolated tissue compartments. What causes the overall population of HIV to shift? And why does the appearance of X4 virus signal the demise of so many T-cells?

From cradle to grave

Choudhary and colleagues from the University of California, Irvine, investigated the effect of HIV infection with an X4 strain on thymocytes, precursors to T-cells that reside in the thymus, a kind of incubator for immature immune cells. [7]

One theory for the accelerated CD4 cell depletion associated with X4 HIV maintains that the virus is capable of killing T-cells while they are still in their thymic cradle. In the experiment, thymocytes were infected with HIV and microarray technology was used to monitor changes in the expression of 22,000 gene products. They also assayed for various indicators of apoptosis. The most significant finding was that HIV infection induced apoptosis through a pathway involving a protein called caspase. This was confirmed by artificially inhibiting caspase, which had the effect of blocking apoptosis in infected cells. These results suggest that if the war between R5- and X4-using HIV comes to the thymus, the impact on CD4 cell production could be very dramatic indeed. There is still much to be learned about how and where HIV causes all the harm it does. Fortunately, we don’t need to understand every detail of HIV pathogenesis to continue developing newer and better therapies.

In vivo studies at Bangkok

At Bangkok, Pfizer presented five posters on its CCR5 blocker, UK-427,857, including results from a 10-day proof-of-concept study. Patients with CD4 counts above 250 cells/mm3 (currently off treatment or treatment-naïve) were randomised to a series of escalating doses or to placebo. Dosing began at 25mg once-a-day (QD) and increased to 300mg twice-a-day (BID), including one arm at 150mg BID taken with food. Monitoring continued for 30 days after treatment was stopped at day 10.

All doses from 100mg QD onward produced mean viral load reductions better than -1.0 log copies/mL. At the 150mg BID dose, food reduced the peak concentration and total exposure (AUC) to the drug by about half, although there was no difference in viral load reduction at that dose whether taken with food or not. This may be because blood concentrations of CCR5 blockers are not as important as how many R5 receptors become occupied by drug molecules and how long they stay. It seems that these drugs tend to stick to their targets and not let go, a quality that could extend the effective potency of a dose by several days. In this study, high levels of receptor saturation were achieved at every dose except 25mg QD.

All persons enrolled were assayed for HIV co-receptor usage phenotype and were required to have an exclusively R5-using strain at time of enrollment.

Of the 66 patients exposed to the drug, 2 experienced an emergence of a dual R5/X4 strain by day 11 of the study. One of these individuals reverted to R5 phenotype by day 40, but the other’s dual phenotype HIV persisted throughout the first 6 months of follow-up. Because the assay cannot pick up sequestered or very small populations of X4-using HIV, the risk of forcing a population shift is evident in this small, initial study. However, in the person whose X4 phenotype persisted, no evidence of accelerated immunological or clinical deterioration has yet been reported. A more detailed presentation of this individual’s case is anticipated at an upcoming conference. Adverse events were mild to moderate and included headache and dizziness. A separate report found no impact on QT interval, the cardiac rhythmic parameter that was perturbed by Schering’s first R5 blocker. [8]

Source: GMHC Treatment Issues, July/September 2004


Abstracts are available at:

1. Bermejo M, PablosJ, González N et al. Impact of CXCL12 production by dendritic cells in HIV infection. XV Intl AIDS Conference, Bangkok. Abstract MoOrA1043.
2. Harrigan PR, Asselin J, Dong W et al. Prevalence, predictors and clinical impact of baseline HIV co-receptor usage in a large cohort of antiretroviral naïve individuals starting HAART. XV Intl AIDS Conference, Bangkok. Abstract MoPeB3117
3. Moyle GJ, Petropoulos C, Goodrich J et al. Prevalence and predictive factors for CCR5 and CXCR4 co-receptor usage in a large cohort of HIV-1 positive individuals. XV Intl AIDS Conference, Bangkok. Abstract WePeB5725
4. Ito Y, Grivel J, Chen S et al. CXCR4-tropic HIV-1 suppresses replication of CCR5-tropic HIV-1 in human lymphoid tissue by selective induction of CC-chemokines. XV Intl AIDS Conference, Bangkok. Abstract MoPeA3057
5. Bonneau KR, Diaz L, Relman D et al. Differential gene expression in primary human CD4+ T cells infected with nonsyncytia-inducing (NSI) and syncytia-inducing (SI) isolates of HIV-1 recovered from the same individual. XV Intl AIDS Conference, Bangkok. Abstract TuPeA4381
6. Valentin A, Morrow M, Yarchoan R et al. Differential effects of TNF on HIV-1 expression: R5 inhibition and implications for viral evolution. XV Intl AIDS Conference, Bangkok. Abstract MoOrA1048
7. Choudhary SK, Powell D, Walker R et al. HIV-1 induces apoptosis in infected thymocytes. XV Intl AIDS Conference, Bangkok. Abstract MoPeA3008
8. Fätkenheuer G, Pozniak A, Johnson M et al. Evaluation of dosing frequency and food effect on viral load reduction during short-term monotherapy with UK-427,857 a novel CCR5 antagonist. XV Intl AIDS Conference, Bangkok. Abstract TuPeB4489

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The UK-CAB receives unrestricted funding from some pharmaceutical companies towards the direct costs of holding four meetings each year. This funding supports the travel and accommodation costs for members to attend from outside London, plus the cost of catering.

The content, programme and agenda for meetings is decided by the UK-CAB steering group in consultation with the wider membership. Funding is unconnected to meeting content.

We believe that manufacturers who currently develop and market medicines have a responsibility to actively engage with advocacy organisations and that HIV positive people and their advocates should be able to directly question manufacturers about the safety and efficacy of their products and proposals for future research.

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