The Ambrose laboratory takes three approaches to studying HIV infection and therapeutics: 1) transmission and prevention of HIV; 2) HIV treatment and drug resistance, including identification of new therapeutic targets; and, 3) persistence of viral reservoirs in vivo. Daily oral pre-exposure prophylaxis (PrEP) using two antiretroviral drugs is effective at preventing HIV transmission in high-risk populations. A concern in using antiretroviral drugs for both treatment of HIV-infected individuals and for PrEP is the potential for transmission or development of drug-resistant HIV isolates during PrEP. The Ambrose laboratory is studying the efficacy of long-lasting PrEP in preventing transmission of HIV, including common drug-resistant strains. In addition, the laboratory is investigating the mechanisms of novel small molecule inhibitors at preventing HIV infection in vitro and in vivo. The Ambrose laboratory is also investigating the differences of HIV infection of macrophages and CD4+ T cells, both critical cell types infected in the host. Understanding these differences will lead to the exploitation of these pathways with novel antiretroviral strategies. Finally, the Ambrose laboratory studies viral diversity and variability, particularly of drug resistance mutations, that develop in blood and different tissues before, during, and after therapy to identify the nature and dynamic properties of persistent viral reservoirs both in and outside of the blood.