Because most adults harbor latent herpes simplex (HSV), HSV infections are common opportunistic pathogens of individuals with acquired immunodeficiency syndrome (AIDS). Recent studies have demonstrated that HSV can also infect the same type of cells infected by human immunodeficiency virus (HIV-1) and furthermore studies using chimeric constructs have demonstrated that HSV can transactivate the long terminal repeat of HIV. While these results suggest that there may be potential interactions between HIV and HSV that are important to the development of AIDS, most of these studies are based upon molecular and immunological data from in vitro studies. Clinical studies on the interactions between these viruses have been based upon serological data and the evaluation of this data has been difficult because of the high incidence of seropositivity for HSV among HIV-1 infective individuals. Furthermore, these studies have not provided any data concerning the mechanism by which HSV may interact with HIV. A possible problem with these clinical studies is that they have focused on determining the levels of antibodies that react with structural proteins of HSV. In this study we plan to do a retrospective study to determine the level of antibodies against proteins, some of which are required for HSV replication, that are expressed early in HSV infections (DNA polymerase, DNase and the 65K DNA binding protein and to correlate the pattern of antibody expression with the clinical course of HIV infection. We also plan to do a prospective study in which we follow the same antibody patterns, isolate HSV from infected individuals and determine the level of resistance of these isolates to the antiviral agents used for chemotherapy in AIDS patients. Furthermore, using polymerase chain reaction and DNA sequencing techniques, we will determine the mutations which accumulate in the HSV DNA polymerase and thymidine kinase genes as a function of time treatment and the antiviral agent used and correlate these data with clinical manifestations of the disease. The significance of this study is that it will provide new methods for predicting the onset of active HSV infections as well as the emergence of drug resistant mutants of HSV so that prophylactic treatment can be administered. Such early intervention may prove to be more effective in limiting the morbidity of the disease.