An ongoing momentum of investigations The history of AIDS research and the contributions of NYU investigators are closely linked. Early in the epidemic, NYU clinicians and scientists would amass a significant list of "firsts" setting the standard for clinical care and research.
In November 1980, we identified and successfully treated a lymphopenic gay man with Pneumocystic carinii, and presented a series of similar patients at the ICAAC meetings in Autumn 1981. We were authors on the initial descriptions of these patients in the New England Journal of Medicine.
Investigators at NYU were the first to identify Kaposi's sarcoma as a manifestation of AIDS and the first to notify the CDC about the prevalence of this cancer among young gay men. NYU scientists were the first to determine that the syndrome is characterized by an immune deficiency.
Early on, investigators here made the discovery that one-third of "healthy" homosexual men in NYC had immunologic abnormalities -- the first indication that large numbers may be affected and that there is an early asymptomatic phase of the syndrome.
After observing virus-like structures in lymphocytes by EM, an NYU pathologist sent blood samples from these early patients to Dr. Robert Gallo, then Virology Laboratory Chief at the National Cancer Institute. These were among the first specimens he examined in his studies that contributed to his isolation of HIV.
In 1984, NYU researchers were the first to receive FDA permission to test ganciclovir for the treatment of cytomegalovirus (CMV) infection. At that point, NYU had treated about 1,000 patients with CMV, 1/6 of the national caseload. Later NYU researchers would lead a national study proving Bactrim is more effective than aerosolized pentamidine in preventing recurrences of PCP. We were the first to elucidate basic mechanisms by which HIV infection can result in thrombocytopenia, and the first to document Kaposi's sarcoma in HIV negative gay men, suggesting a second transmissible agent.
Our investigators, in collaboration with those at Rochester, performed the Phase I/II trial of ddI that defined the dose and toxicities of this drug. Continuing its leadership in drug trials, NYU led a four-site trial that demonstrated for the first time that 3 drug combination therapy, (with indinavir, 3TC and ZDV) is able to suppress HIV-replication, as measured by plasma viremia, below the level of detection in a majority of patients for many years. Subsequently our adult and pediatric clinical trials units have been participants in the evaluation of essentially all antiretroviral agents currently in use.
Scientists at NYU determined the structural biology of the binding of the HIV protein Rev to the Rev responsive element of HIV RNA, delineated the role of multiple chemokine receptors as a second receptor for HIV, and described the ability of DC SIGN to bind and protect HIV on dendritic cells as they transport and present HIV to CD4 T cells.
More recently they have investigated the roles of mDCs and pDCs in HIV pathogenesis, and the function of T regulatory cells, and factors governing the formation of Th-17 cellsNYU's pediatricians have also played a major role in AIDS since the early years of the epidemic. They were the first to describe the correlation between maternal viral burden and HIV transmission. Pediatricians here also described the acquisition and loss of specific immune responses in HIV-infected children.
In addition, the Pediatric AIDS Clinical Trials Unit here participated in the ACTG 076 study which pioneered the standard of care to prevent perinatal transmission in pregnant HIV+ women with administration of zidovudine (AZT). Discoveries at NYU have led to changes in immunization practices and in guidelines for PCP prophylaxis for children with HIV. NYU's pediatric clinical services and family outreach programs are among the most comprehensive in the nation. We now have young mothers who were infected at birth and have grown up to have their own uninfected children.
Patients and patient specimens are essential for the study of HIV disease, and NYU investigators were initially motivated to devote their talents to the study of the disease because of the abundance of clinical material. This remains true since the NYU clinical faculty currently follow over 4,000 HIV-infected patients, and our investigators can recruit from the many additional thousands of HIV-infected individuals in the New York City metropolitan region.