back to today's front page

for immediate release

BASIC SCIENCE TRACK 'A' HIGHLIGHTS

ENGLISH     FRENCH

(GENEVA, SWITZERLAND)- Thursday, 2 July, 1998 - Presentations in Track A, the Basic Science Track of the 12^th World AIDS Conference, will address the long-term effect of combination antiretroviral therapy, the prospects that HIV can be "eradicated" from protected sites in the body, and new data on the spread of drug-resistant HIV. Other Track A sessions will discuss the scientific and therapeutic significance of natural immunity to HIV infection, the meaning of decreased plasma viral load in terms of health, longevity, and infectiousness, and how therapies and vaccines can more effectively target the virus.

Also on the scientific agenda in Geneva: new leads in prospects for molecular targets for antiviral therapy, important new research on the role of coreceptors in HIV infection and illness, and work on many aspects of viral replication that has the potential to open doors in research for new treatments.

"The previous World AIDS Conference, in Vancouver in 1996, presented exciting data, but raised at least as many questions as it answered," said Dr. Mark Wainberg of Montreal's McGill AIDS Centre, and Chair of Track A. "Vancouver ended with a great deal of hope, but with many significant questions left unanswered. We're now in the era of incremental steps in HIV/AIDS research. We don’t have the final answers to our questions, but the science to be presented at the Geneva meeting significantly advances our knowledge in each of these important areas."

Among many noteworthy talks and presentations included in Track A of the 12^th World AIDS Conference are those addressing the following subjects:

Chemokine Research

The role of chemokine receptors has been seen as increasingly important in the future of drug development for HIV. Session A12 "Chemokines and Receptors 1", (Monday, 11.00-12.30, Session Hall IV) includes research discussing the correlations between genetic subtypes of HIV-1 and chemokine usage. This research opens the possibility that genetic subtypes of HIV may differ in

important biological properties such as virulence, tissue tropism and transmissibility, and may ultimately influence clinical progression of HIV illness.

In addition, a noteworthy Late Breaker, "A Trans-Receptor Mechanism for Infection of CD4-Negative Bystander Cells by HIV-1" (Friday, 08.30-10.30, Arena) describes a novel mechanism by which CD4^- cells may be permissive for infection in tissue settings in which they comingle with CD4⁺ cells. This mechanism may contribute to disease pathogenesis by expanding the range of susceptible targets to include CD4^- or CD4-low cells that may then serve as reservoirs for latent or replicating virus.

Natural Immunity

Several papers presented in Track A offer important new information on natural immunity to HIV, and its possible implications for prevention and treatment.

Session A13, "Chemokines and Receptors II" (Monday, 13.00-14.30, Hall IV) includes the paper "Mechanism of Transdominant inhibition of CCR5-Mediated HIV-1 infection by ccr5(tri)32" which presents important new data on natural immunity to HIV infection. By studying the relationship between CCR5 mutation and full or partial immunity to HIV, or delayed disease progression, scientists hope to better understand these "resistance receptors," and to develop drug molecules that will antagonise their function to confer some protection from HIV infection.

Session A31, "Humoral Immunity", (Wednesday, 11.00-12.30, Hall IV) includes an important Kenyan study of sex workers who remain uninfected with HIV-1 despite repeated exposures. The research abstract, titled "HIV-1 Specific Mucosal IgA in a Cohort of Resistant Kenyan Prostitutes" found HIV-1 specific IgA in the genital track of most highly-exposed uninfected subjects, as well as in a minority of seronegative controls who had some HIV risk. These data suggest that mucosal virus-specific humoral responses play a role, independent of host cellular responses, in resistance to HIV-1. Researchers hope that, by better understanding the factors that create resistance to HIV in some individuals, they will be able to create drugs that mimic this response in individuals who are not resistant.

Viral Load

Session A21, "Viral Assays and Diagnostics" (Tuesday, 11.00-12.30, Hall IV) includes a study entitled "Plasma and Genital Tract Viral Load and STD's in Early HIV Infection", which assesses the relationship between viral load in plasma and semen and the impact of antiviral chemotherapy on semen and female genital fluids. This study is considered to be a very important from a public health standpoint. While extensive research has been performed on the significance of viral load in the bloodstream, far fewer studies have examined the significance of virus in genital fluids, which may impact both transmissibility and the long-term health of the infected individual.

Viral load monitoring is also addressed in the Late Breaker paper "Monitoring HIV Therapy in Specific Cells Using Ultrasensitive Fluorescence in Situ Hybridization" (Friday, 08.30-10.30, Arena), which describes a new assay to monitor efficacy of antiretroviral therapy in specific cell populations. Preliminary results indicate that this assay may identify changes in viral production prior to plasma viral load.

ART – Long-Term Effectiveness, When to Start

Promising data on triple combination therapy have been reported at the 11^th World AIDS Conference in Vancouver in 1996, and at other scientific meetings. However, most have included the proviso that longer-term data is needed. Session A14, "Immune Reconstitution Following ART" (Monday, 15.00-17.00, Hall III) includes a presentation titled "Prolonged Suppression of HIV-1 Viremia Results in Profound but Incomplete Enhancement of Anti-HIV-1 CTL Responses in Advanced Infection". This talk will present two-year data on patients with advanced HIV infection who received combination drug therapy (IDV, ZDV, 3TC). The study indicates that appropriate combination antiretroviral therapy continues to impact positively on immune responsiveness over the length of this study.

A significant question in HIV treatment is when to begin antiretroviral therapy (ART). While many researchers and physicians have advocated treating the virus as early in infection as possible, others have expressed a more cautious approach, urging the delay of aggressive treatment in many cases. Also part of Session A14, the paper "Initiation of Antiretroviral Therapy During Primary HIV Infection is Associated with Rapid Stabilisation of the TCR Vb Repertoire and Reduction of CD8+ T Cell Oligoclonality", which, while not answering all questions, suggests that a number of potential benefits are associated with beginning treatment at the earliest possible stages.

Viral Reservoirs

With advances in ART, the eradication hypothesis has focused attention on latent reservoirs of HIV infected T-cells in all parts of the body. Session A26, "HIV Pathogenesis" (Tuesday, 15.00-17.00, Session Hall IV) includes a study of the rate of turnover of latent viral reservoirs in patients on HAART titled "Latent Viral Reservoirs in Patients on Highly Active Antiretroviral Therapy: Implications for Virus Eradication". This study indicates that latent reservoirs are established very early in primary HIV-1 infection, and that these reservoirs remain extremely stable, with no measurable decay, during the first two years of HAART therapy. The potential to reach these latent reservoirs is the subject of ongoing study.

On Wednesday, in Session A33, "Viral Reservoirs" (Wednesday, 13.00-14.30, Hall VII) Drs. Peter Biberfeld, Melissa Pope, and Jan Orenstein will also discuss the protected polls of HIV inside the body that complicate efforts to treat.

Viral Mutation

Turning to the question of HIV-1 subtypes and the spread of the disease, a study presented in Session A35 (Molecular Epidemiology, Wednesday 15.00-17.00, Hall IV) titled "Molecular Epidemiology of HIV-1 Genetic Subtypes in West and Central Africa" indicates how quickly HIV-1 can mutate, evolve into new forms, and spread. This research is significant not only because of the increased understanding it affords of HIV’s activity, but also has significance in the development of procedures to screen blood supplies for a rapidly evolving virus.

Vaccine Research

As HIV continues to spread through the both the developed and developing world, increasing attention is being paid to the need for, and the unprecedented challenges surrounding, the development and testing of HIV vaccine candidates. Session A 41, "Vaccine Trials in Humans" (Thursday, 11.00-12.30, Hall VII) presents the latest data on HIV vaccine development, and will point the way for future directions in research for what may be the most potentially promising form of global HIV prevention.

Vaccine development is also the subject of Session A45, "Vaccines: Animal Models and Development" (Thursday, 15.00-17.00, Hall VI), which will include discussions of the viability of new vaccine approaches, including the prospects for development and testing of live attenuated HIV candidate vaccines. Advances in vaccine development will also be addressed in the Late Breaker session (Friday, 08.30-10.30, Arena) titled "Modulation of Protective Immunity in Macaques Using Molecular Adjuvants," which found that when HIV-DNA vaccines was combined with cytokine DNA rhesus macaques were partially protected from a challenge with SHIV, and that the level of neutralizing antibodies was not a correlate of protection.

CNS Involvement

Because many of the newer HAART regimens penetrate the brain poorly, if at all, research designed to study the possibility of eradicating HIV from protected reservoirs has focused considerable attention on the central nervous system. Of particular interest is a study presented in Session A43, "Pre-Clinical Drug Development" (Thursday, 13.00-14.30, Hall VII) titled "Abacavir (1592, ABC) Prevents Spread of HIV-1 in Brain Tissue of SCID Mice with HIV-1 Encephalitis".

A Late-Breaking abstract describes a successful trial of human nerve growth factor for HIV-associated sensory neuropathy - a complication of HIV infection which so far has proved refractory to treatment. The abstract, "Trial of Recombinant Human Nerve Growth Factor for HIV-Associated Sensory Neuropathy" (Friday, 08.30-10.30, Arena) presents phase II study data from the first study of the use of neurotrophic factor in HIV-infected patients.