Lisa M. Frenkel, MD

Clinical and Research Background

The Frenkel Group performs translational and basic laboratory research focused on HIV drug resistance (DR) and HIV persistence.

Her laboratory aims to understand the establishment and dynamics of DR reservoirs and whether testing for HIV DR prior to antiretroviral therapy (ART) modifies outcomes (Lancet HIV, 2020; PMID 31818716) and how DR impacts mother-to-child-transmission of HIV (Clin Infect Dis, 2021; PMID 34467974). The Frenkel lab has participated in the NIH International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) since 1989 and serves as the primary HIV-DR genotyping lab for all US sites and the reference lab for international IMPAACT studies. Dr. Frenkel also is a member of the UNAIDS expert panel on HIV. With UW Bioengineers, the Frenkel lab develops inexpensive methods to assess HIV drug resistance (EBioMedicine 2019; PMID 31767540). Current HIV DR projects focus on: (1) HIV DR of non-B subtypes to the globally recommended ART (tenofovir + lamivudine + dolutegravir (TLD)), and with abacavir instead of tenofovir in young children; and (2) the development of a economical assay to rapidly detect “virologic failure” (i.e., HIV RNA load >500-1000 copies/mL plasma), and in specimens with failure, detect HIV DR at cost of reagents ≤$10.00/test in <2 hours; supported by two R01 and an IMPAACT award.

The Frenkel lab’s research on mechanisms underlying HIV persistence despite effective ART has introduced novel concepts to the field: (1) That low-level viremias during ART are primarily comprised of virions with identical env and pol sequences suggesting production by clones of infected cells (Journal Virology, 2005; PMCID 1181593); (2) That cells with identical viral sequences appear to increase during ART, further supporting clonal proliferation of cells with provirus (Journal Virology, 2013; PMCID 3554159); (3) That multiple cells have proviruses with identical HIV integration sites into genes, proof of clonal cell populations, which increase during suppressive ART and which tend to persist in genes that control immune functions, the cell cycle or cancers (Science, 2014; PMID 25011556); and (4) That during effective ART a subset of HIV infected clones persistently produce virions at low-levels, including variants that contribute to viral rebound when ART is stopped, suggesting that clones that actively produce virus escape immune surveillance and serve as HIV reservoir of persistent infection capable of repopulating the host if ART is suspended (PLoS Pathogens 2000; PMID 32841299). Current projects on HIV persistence include studies of: (1) HIV effects on the outcome of human papilloma virus infections in Ugandan women with uterine cervical dysplasia; (2) differences in HIV reservoirs of South African children and their mothers; and (3) identification of HIV reservoirs that rebound upon suspension of ART and the factors that select for persistence of these reservoirs.