The SCOPE Cohort
The overarching objective of SCOPE is to provide access to a group of well-characterized contemporary HIV-infected patients of diverse demographic and clinical status to all UCSF-GIVI CFAR researchers as well as investigators from outside institutions.
The field sites for SCOPE are the HIV/AIDS clinic of the San Francisco General Hospital (SFGH) Positive Health Program (directed by CFAR Investigator Dr. Diane Havlir), where both Core Directors Deeks and Martin practice, and the Infectious Diseases Clinic at San Francisco Veterans Affairs Medical Center (SFVAMC), where it is facilitated by Dr. Harry Lampiris. In the initial phase of enrollment in SCOPE, participants had to be at least 18 years old, infected with HIV for more than 6 months, and attending either the SFGH or SFVAMC HIV/AIDS clinic. As a cohort conceived in the contemporary treatment era, SCOPE necessarily had to contend with substantial heterogeneity in terms of antiretroviral therapy (ART) and treatment response. To address this, recruitment was initially stratified by treatment exposure and response in order to ensure sufficient numbers of participants in each broad group. The ratio of participants across groups was established to approximate that of most urban clinic settings in the United States at that time. The following groups were enrolled:
- Untreated: Patients who had never been treated with antiretroviral agents or who had been off therapy for at least 6 months
- Treated, virologic controllers: Patients who had an undetectable plasma HIV RNA level ("viral load") for the previous 6 months while using combination ART
- Treated, virologic non-controllers: Patients who experienced "virologic failure", defined as having a detectable plasma HIV RNA level (500 copies/ml) for the previous 6 months despite treatment with combination ART
Although SCOPE was initially intended to be a fixed cohort with one cycle of recruitment and subsequent follow-up of that fixed group, it was recognized early on that allowing for a dynamic cohort with additional cycles of new recruitment based upon the interests of the CFAR community would create a far more flexible platform to serve a greater number of investigators and maintain pace with changing scientific priorities. Most recently, a concerted effort was made by the Core Directors to respond to the growing interest of CFAR investigators to identify infected individuals who might provide critical insights as to how HIV infection might be naturally contained. These rare individuals who by virtue of either limiting virologic replication and/or preventing immune system destruction present the "natural experiment" proof of concept that human hosts can effectively contain HIV. Two overlapping groups have been targeted:
- Immunologic long-term non-progressors: Patients who have documented HIV infection for at least 10 years without the occurrence of HIV-related disease manifestations and without any decline of CD4+ T-cell counts outside of the normal range (i.e., CD4+ T-cell count >500 cells/mm3);
- Spontaneous ("elite") virologic controllers: Patients who are untreated and who have at least 3 documented plasma HIV RNA levels <2,000 copies/ml over at least a 12-month period. A subset of these subjects has persistent plasma HIV RNA levels <75 copies/ml.
Finally, in the past year, HIV-uninfected "healthy" subjects have been enrolled in SCOPE as a valuable comparator to the HIV-infected individuals.
Today, SCOPE can be best described as a dynamic cohort whose composition is in large part dictated by the interests of the CFAR research community. It maintains as its heart participants with the most common clinical characteristics of HIV infection (e.g., treated with or without undetectable HIV RNA level) but also has the ability to oversample specialized groups of participants based upon the interests of CFAR researchers. The infrastructure-based funding for SCOPE allows for this flexibility, something that would be less feasible within conventional single-hypothesis-based cohorts. As such, SCOPE is not intended to be a random sample of the community or even of a clinic. Nonetheless, of the 1443 subjects enrolled, there is a diverse distribution of racial/ethnic background and gender that reflects HIV infection in California; almost 50% of subjects are non-white and 12% are women.
Since the SCOPE cohort's inception, in addition to questionnaire-based data, the Core has distributed 26,952 biological specimen aliquots (as of April 2010) to collaborating researchers.