UCLA Center for HIV Prevention Research's (CPR) strategy on studying tissue, as well as blood, pushed a paradigm-shifting focus in the HIV field by emphasizing the critical role of direct tissue-based translational research efforts. These now have their place in the developmental pipeline often before more focused non-human primate studies.
CPR research projects have included acquiring human tissue/fluid/blood samples in studies of:
It is apparent that these focused, inter-related research areas have been possible due to mutually-supportive, collaborative research teams across the globe. Over the past ten years, the teams have:
These investigative efforts have been designed with an inherent component of using both healthy and inflammatory controls for HIV-specific studies/trials of HIV individuals with high plasma viral load on no therapy versus those fully suppressed on combination therapy. These study cohorts provide our group and collaborators with infectious controls (HIV) for IBD-specific studies and vice versa. The stability of the research assay templates and translational clinical trials group enables CPR/collaborators to no move into the area of therapeutic vaccine for not only HIV but also cancer and immunotherapy for cancer, HIV as well as autoimmune disorders.
The lab has also increased the scope of its research: in addition to ongoing investigation of HIV vaccines, CPR's current portfolio includes assays on the effectiveness of new prevention strategies, specifically rectal microbicides. Microbicides, the prime focus of our prevention therapy research, are a cornerstone of the global strategy to combat HIV transmission. Microbicides are a chemical substance, typically a lubricant, cream or gel. They contain drugs which can significantly prevent or reduce sexually transmitted infections, including HIV, when applied locally to the vagina or rectum
Microbicides function by reducing the risk of infection per sexual act. They are the first new preventions against HIV developed since condoms and other behavioral modifications. The rate of new infections suggests that these "liquid condoms" would fill an important prevention gap for men and women who cannot successfully negotiate mutual monogamy or male condom use.
CPR is among the few groups worldwide currently developing these innovative therapies for the rectal area. To date, the focus of microbicide studies has been on vaginal agents, with limited research on rectal formulations. Because the vagina and the rectum differ greatly in ecology and structure, they will require different product formulations. In addition, the rectum is far more vulnerable to HIV transmission than the vagina, and anal intercourse is between 10 and 200 times more likely to result in transmission of HIV than vaginal intercourse.
HIV introduces an acute inflammatory state in the gastrointestinal lining years before it leads to immune deficiency. CPR is investigating anti-inflammatory components, both for patients already taking anti-retroviral therapy (ART) and with volunteers not presently on ART. Although not anti-viral, these anti-inflammatory agents would reduce the inflammatory milieu of the gastrointestinal lining.
Despite the effectiveness of ART, HIV-associated diarrhea remains a significant symptom. CPR is studying the possibility that this may result from imbalances in the intestinal flora. Microbial food supplements, or probiotics, are being considered as a supplement that could improve intestinal microbial balance and decrease symptoms of diarrhea.
CPR maintains an aggressive role in HIV vaccine research. We are one of the leaders in analyzing whether immune responses actually occur where and when the virus first enters the body, and how vaccines may prime the mucosal surfaces to be activated against HIV during exposure. We recognize that an acceptable HIV vaccine is many years away; a combined approach of vaccines and microbicides is the only tenable scientific response to prevent further spread of HIV.