Throughout history, scientists have developed vaccines using their understanding, however rudimentary, of what causes protective immunity against a targeted disease. With HIV, however, an understanding of protective immunity is lacking, hampering the development of a vaccine and other drugs to combat the virus. 
 
A subset of women who apparently are resistant to the virus may provide scientists with the genetic and immune system information they need to advance vaccine and drug development. Since 1985, investigators have tracked groups of commercial sex workers in Kenya who do not become infected with HIV despite repeatedly having sex without condoms. If investigators can understand what constitutes and results in protective immunity against HIV, they may be able to replicate it through vaccines. 
 
Dr. Plummer's team is conducting an exhaustive analysis of the immunologic and genetic factors that mediate HIV resistance in the women, with the goal of gaining a more complete understanding of what constitutes protective immunity against HIV infection. 
 
Investigators are conducting a number of studies in which preliminary results suggest that resistance to HIV infection likely results from a specific set of immunologic and genetic factors acting alone or in concert. Studies also suggest that resistant women have altered innate immune responses that may affect the generation of protective adaptive responses or cause HIV replication to be hindered so that adaptive responses have room to develop. Data suggest that resistant women are biologically distinct and have unique expression patterns of immune response genes. 
 
Dr. Plummer's team notes that their work is correlative in nature. Proving causation and evaluating the complex, likely multi-factored mechanisms that may be involved in resistance will require a longitudinal, prospective analysis. Investigators have increased enrollment in a Kenyan sex worker clinic and begun the collection of samples necessary for this component of the study.