Unless otherwise indicated, please delay release of the information contained in the summaries until the time of the presentation.
Two inhibitors are better than one
Note: Embargoed for release until Saturday, July 6, 2002 at 8:00 a.m. Eastern time.
Protease inhibitors are powerful HIV drugs, but some patients begin to fail to respond to one or more of the drugs over time. NIAID's AIDS Clinical Trials Group (ACTG) study ACTG 398 was a placebo-controlled study designed to see if treatment regimens using two protease inhibitors are superior to those using only one such inhibitor among patients who have previously failed to respond to that class of drugs. The study, which will appear July 6, 2002, in the online edition of The Journal of the American Medical Association (JAMA), is the first to show that therapy with dual protease inhibitors produces more pronounced virus suppression than single-inhibitor regimens in people with a history of HIV protease inhibitor failure. JAMA will host a media briefing describing this and other studies.
Recent herpes simplex virus 2 is a risk factor for HIV infection in India
Although several studies have identified genital ulcers as a major risk factor for HIV infection, little is known about the effect of acute herpes simplex virus type 2 (HSV-2) on HIV risk. Researchers from Johns Hopkins University in the United States and the National AIDS Research Institute in Pune, India, will report that recent HSV-2 infection is a major independent risk factor for HIV acquisition among Indian patients with sexually transmitted diseases (STD). The data suggests that ulcers formed during acute HSV-2 infection may help facilitate HIV infection, and that primary prevention of HSV-2 might reduce the risk of contracting HIV among STD patients.
Anti-HIV antibodies influence HIV evolution
The ways in which antibody responses to initial HIV infection affect the nature of the virus are poorly understood. Measuring those antibody responses has been difficult, but now a team of U.S. scientists has used a novel HIV entry assay to observe how the virus envelope changes in response to neutralizing antibodies. Researchers from the University of California at San Diego teamed with scientists from ViroLogic in South San Francisco to conduct the study. The investigators found that most patients rapidly produced strong neutralizing antibody responses against HIV. As the infection progresses, however, each sequential form of the virus envelope increasingly escapes detection. The study shows a remarkable degree of virus escape from neutralizing antibodies and suggests that those antibodies can have previously unappreciated affects on HIV evolution. The data have important implications for HIV vaccine development.
World's largest preventive HIV vaccine trial
A safe, effective HIV/AIDS vaccine remains the ultimate goal of HIV research.
On Monday, July 8, scientists representing an international research collaboration will brief the press on the largest community-based, preventive HIV vaccine trial ever planned. The trial, a collaboration between scientists from the United States and Thailand, will be the first large-scale
test of a prime-boost vaccine regimen, in which two different vaccines are administered to stimulate a more powerful immune response. The study will be conducted in Thailand, will involve 16,000 volunteers, and is expected to last for more than five years.
Researchers dissect HIV to find T-cell stimulating proteins
Cytotoxic T lymphocytes (CTL) play a key role in controlling HIV infections, but a comprehensive analysis of the parts of HIV recognized by those cells has not been conducted. Using a system that allows rapid screening of all HIV gene products, researchers from Massachusetts General Hospital have examined each of those gene products for its ability to initiate CTL responses. The investigators discovered that all HIV proteins can serve as CTL targets. The Gag proteins, which make up the major components of the virus core, are the most frequently targeted, but the anti-HIV immune response is highly variable in different groups of people.
HIV in blood has multiple effects
HIV viremia has many effects on infected individuals. Those effects include multiple alterations in immune responses, selective dysfunction of several organ systems, and the maintenance of a persistent HIV reservoir. During his plenary lecture, NIAID Director Anthony S. Fauci, M.D., will provide an overview of the work conducted in his laboratory on the ability of HIV to selectively activate host genes that induce expression of virus as well as those that create a permissive environment for HIV infection. He will describe in detail how HIV viremia can induce changes in both proliferating and resting T cells, and how those changes have implications for HIV treatment.
Multidrug HIV treatment regimens: order in which drugs are used and how drugs are combined matters
Highly active antiretroviral therapy (HAART) uses combinations of potent anti-HIV drugs to suppress the virus in people with HIV/AIDS. The effectiveness of different regimens wanes with time, however, causing physicians to switch to new drug combinations. But which combinations provide the best benefits for people who were not previously on antiretroviral drugs is poorly understood, as is the optimal order in which different regimens should be used.
NIAID designed study ACTG 384 to address those questions. Different three-drug regimens were used sequentially in different orders, and patient groups were assessed for the time period between the start of treatment until failure of the second three-drug regimen. The study showed that how drugs are combined is important. A combination of zidovudine (ZDV), lamivudine (3TC), and efavirenz (EFV) appears to be particularly beneficial compared with other three-drug regimens, including the similar combination of ZDV, 3TC and nelfinavir (NFV). Researchers found no evidence of a difference between three-drug regimens using stavudine (d4T) and didanosine (ddI) combined with either EFV or NFV. All combinations were able to strengthen the immune system, as measured by CD4+ T-cell counts, and the risk of death or illness was very low.
ACTG 384 also addressed whether four-drug regimens differed from sequential three-drug combinations. The study showed no evidence that single four-drug regimens were superior to sequential three-drug therapies for the overall study endpoint. However, when comparing time to failure of the first regimen used, four-drug regimens appeared better than some three-drug regimens, but not better than ZDV+3TC+EFV. Significant toxicities were greater in arms containing d4T in combination with ddI than in those containing ZDV and 3TC.
The initial observations indicate that ZDV+3TC+EFV is a particularly useful regimen for initiating therapy in HIV-infected individuals who have not previously received antiretroviral drugs. The mechanisms underlying this benefit are still under investigation.
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, illness from potential agents of bioterrorism, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Press releases, fact sheets and other NIAID-related materials are available at the NIAID Web site at http://www.niaid.nih.gov.