ARRA IMPACT REPORT:
Basic HIV Research
Public Health Burden
Although progress has been made in the global fight against HIV/AIDS, the epidemic continues to challenge the United States and the international community, with approximately 50,000 new HIV infections each year in the United States and an estimated 34.2 million people living with HIV worldwide.1 NIH is committed to investing in research that will ensure an end to the HIV/AIDS epidemic.
Fundamental research on HIV disease development, or pathogenesis, will improve our understanding of the virus’s life cycle, host-viral interactions, and mechanisms of viral transmission and disease progression. Knowledge gained through this research will enhance our ability to develop novel therapeutic and vaccine strategies for the treatment and prevention of HIV/AIDS. ARRA funds were used to expand studies aimed at understanding HIV transmission and disease progression, develop models to test the safety and delivery of microbicides to prevent HIV transmission, support additional staff to conduct studies, and train the next generation of scientists.
Characterizing Mutations in HIV-1 Envelope Proteins to Study Viral Transmission & Disease Progression: A collaboration between researchers from the University of Nebraska and Harvard Medical School has implemented next-generation DNA sequencing technology to characterize mutations in the envelope glycoprotein of simian-human immunodeficiency virus (SHIV), a model for studying HIV transmission and pathogenesis, in infected non-human primates. The researchers compared SHIV-infected animals that had progressed to disease and those that had not. They found common, recurring mutations in both cases, suggesting a common evolutionary pattern and selection pathway for the HIV-1 envelope during disease progression. A better understanding of the factors that select for these changes will help in developing strategies to prevent disease progression.2
Antiretrovial Therapy and HIV Viral Shedding: ARRA-funded investigators at the Boston University Medical Campus investigated whether shedding of HIV into the seminal fluid can occur even in the presence of effective highly active antiretroviral therapy (HAART) and resulting viral suppression. The researchers observed a high prevalence of HIV in the semen of sexually active men who have sex with men (MSM) on HAART, and the presence of HIV in seminal fluid was associated with other sexually transmitted infections and genital inflammation. These findings suggest that low-level HIV shedding in seminal fluid of MSM who are receiving HAART could potentially pose a risk for HIV transmission, despite effective HAART treatment and low blood HIV levels.3
GB virus C (GBC) and HIV Co-infection: Researchers at the University of Iowa used ARRA funding to expand their ongoing research to better understand the apparent protective effect of GB virus C (GBV-C) infection on the progression of HIV in people coinfected with the two viruses. Co-infection with GBV-C, a virus that is not known to cause any disease, is common in HIV-infected individuals. The researchers found that GBV-C appears to inhibit specific immune signaling pathways and immune activation, which is a key process in HIV disease progression. In addition, the presence of GBV-C in the bloodstream was found to be associated with a reduction in programmed cell death of activated T-cells (a type of immune cell). These GBV-C–associated T-cell effects could contribute to the observed protective effect of GBV-C co-infection in HIV-infected individuals.4
Bone Marrow Cells and Latent HIV Infection: Investigators at the University of Michigan used ARRA funding to expand their staff and enhance their genome sequencing capacity to augment one of the specific aims of their research. The goal of this research was to examine whether bone marrow is an important reservoir of cells latently infected with HIV; these reservoirs could contribute to viral persistence. The investigators found that certain bone marrow cells are able to harbor latent provirus in HIV-positive individuals who are receiving HAART and have undetectable blood levels of HIV. Latent infection of these long-lived cell types may create a significant barrier to HIV eradication. Thus, further efforts to better understand this viral reservoir are needed.5
Developing an HIV-1 infection Model: Researchers at the Aaron Diamond AIDS Research Center in New York used ARRA funding to analyze the activity of proteins that facilitate viral persistence in non-human primates and to develop novel chimeric, or hybrid, viruses based on HIV-1. Their ongoing work includes testing the utility of these chimeric viruses as an HIV-1 infection model. If successful, this work will lead to improved animal models for HIV-1 infection and will considerably facilitate the development and testing of drug and vaccine interventions for the disease.6
Hepatitis C Virus (HCV) and HIV Co-infection: Investigators from the University of Southern California used ARRA funds to expand their research team in order to further evaluate the role of hepatitis C virus (HCV) on immune activation. In a series of studies, the researchers examined the relationship between T-cell activation, natural killer cell activation, host genetics, and HIV disease progression. Their findings suggest that HIV disease is affected by co-infection with HCV, with heightened immune activation leading to an increased risk of progression to AIDS; that coinfected patients may benefit from earlier treatment; and that certain host genetic factors associated with HIV disease progression may be related to immune activation.7
Contributing NIH Institutes & Centers
- National Institute of Allergy and Infectious Diseases (NIAID)