Lisa M. Frenkel, MD

Over the past 30 years, our group, in collaboration with colleagues in Kenya, Mozambique, Peru, South Africa, Thailand, Uganda and the United States, has conducted studies to address practical questions related to the prevention of HIV-1 infection in infants, mechanisms leading to HIV-1 shedding in breast milk and genital tract of adults, treatment of drug-resistant virus and mechanisms underlying the persistence of HIV infection despite effective antiretroviral treatment. Additionally, we have developed economical assays to improve the management of HIV infection accessible to resource-poor communities.

When studying transmitted resistance from HIV-infected mothers to their children, our group uncovered laboratory errors that refuted the concept of transient HIV infection occurring in infants (Science, 1998; PMID9582120). Findings from this study underscored the importance of meticulous Laboratory Quality Assurance in research. Our group has operated a CLIA Laboratory for >18 years primarily performing assays NIH IMPAACT Network.

Our laboratory located within SCRI found evidence and later provided proof that proliferating cells have a major role in sustaining the HIV reservoir despite effective treatment (J Virol 2005, PMID16014925) (Science 2014, PMID25011556).

More recently we have shown that HIV-infected clones fuel persistent low-level viremia during antiretroviral treatment (ART) and rebound viremia following ART suspension (PLoS Pathog 2020, PMID32841299). We described that HIV is integrated disproportionately into genes that control immune functions, the cell cycle, cancers or pathways controlling T-regulatory cells (J Infect Dis 2017, PMID28520966) and other pathways depending on if ART is initiated during acute or chronic HIV-1 infection (J Clinic Invest, accepted 2023). These finding led to investigations of HIV-1 integration on CD4 cell function (J Immunol 2022 PMID35264460) and current projects focused on (1) effects of integrated virus on high-risk HPV cervical infections, and (2) immune tolerance in HIV infected infants.

Our research on HIV drug resistance has defined reservoirs and effects of mutant codons (Clin Infect Dis 2010, PMID20377404) and the utility of point mutation assays in screening to diagnose HIV drug resistance (Lancet HIV 2019, PMID32386719). Our current studies aim to (1) define the mutant codons associated with failure of dolutegravir-based treatments, (2) develop inexpensive assays to detect these mutations in low-resource settings and (EBioMedicine 2019 PMID31767540 and AIDS 2020 PMID32205723), and (3) define the risk of genotypic HIV resistance for mother-to-child HIV transmission and treatment outcomes (Clin Infect Dis 2021, PMID34467974).