Dara Lehman is a Senior Staff Scientist that conducts her own NIH-funded research projects within Julie Overbaugh’s lab in the Department of Human Biology at Fred Hutch. She is also an Affiliate Associate Professor at the University of Washington in the Department of Global Health. Research projects in the Lehman lab are at the interface of basic science and epidemiology - including studies of viral dynamics, viral reservoirs, drug resistance and virome transmission in cohorts of women and infants in Kenya. Projects involve long-standing international collaborations with epidemiologists, clinicians, biostatisticians and bioinformatic experts.
HIV-exposed uninfected infants have increased morbidity and mortality rates compared to HIV-unexposed infants. We hypothesize that this is in part due to the diversity of all viruses (virome) present in the mother that can be transmitted to their infant - which may differ in women with and without HIV infection. We aim to understand the impact of maternal HIV infection on virome acquisition in infants using samples from retrospective cohorts as well as a new prospective Kenyan cohort that will allow us to sample both the mother and infant over time. We are characterizing mother-child virome interactions to test the hypothesis that perturbations in the maternal virome, due to the effects of HIV infection including CD4 count and antiretroviral use, impact the composition of the infant virome. Further, we will determine associations between virome and health outcomes in infants. Alterations within these microbial communities during early development may have long term health impacts.
During HIV infection, the virus stably integrates in long-lived cellular reservoirs that are established within days of infection and persist despite continuous antiretroviral therapy (ART). Initiating ART at HIV diagnosis has been shown to limit viral reservoir size, reduce immune activation and improve treatment outcomes, including increasing the incidence of post-treatment viral control. However, early treatment alone does not insure low reservoir size or likelihood of post-treatment control. Other factors, such as host immune responses to HIV infection, which change with age of HIV acquisition, may play a role in reservoir containment. We hypothesize that levels of immune activation, which impacts available target cells, HIV-specific antibodies that act by killing infected cells, and NK cell repertoire, which was recently linked to HIV susceptibility could play a role in HIV reservoir establishment and decay. This study aims to elucidate longitudinal HIV reservoir dynamics, size and decay as well as immune factors that influence the reservoir using unique specimen repositories from ART-treated Kenyan infant and child cohorts with 5-10 years of follow-up.
Selected publications are listed below. For a complete list of publications, visit Dara's NCBI bibliography.
Stoddard CI, Sung K, Yaffe ZA, Weight H, Beaudoin-Bussières G, Galloway J, Gantt S, Adhiambo J, Begnel ER, Ojee E, Slyker J, Wamalwa D, Kinuthia J, Finzi A, Matsen FA 4th, Lehman DA, Overbaugh J. Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers. Nat Commun. 2023 Aug 11;14(1):4864. doi: 10.1038/s41467-023-40554-w. PMID: 37567924; PMCID: PMC10421871.
Neary J, Fish CS, Cassidy NAJ, Wamalwa D, Langat A, Ngugi E, Benki-Nugent S, Moraa H, Richardson BA, Njuguna I, Slyker JA, Lehman DA, John-Stewart G. Predictors of intact HIV DNA levels among children in Kenya. AIDS. 2023 May 1;37(6):871-876. doi: 10.1097/QAD.0000000000003499. Epub 2023 Jan 30. PMID: 36723512; PMCID: PMC10079608.
Cassidy NAJ, Fish CS, Levy CN, Roychoudhury P, Reeves DB, Hughes SM, Schiffer JT, Benki-Nugent S, John-Stewart G, Wamalwa D, Jerome KR, Overbaugh J, Hladik F, Lehman DA. HIV reservoir quantification using cross-subtype multiplex ddPCR. iScience. 2022 Jan 21;25(1):103615. doi: 10.1016/j.isci.2021.103615. eCollection 2022 Jan 21. PubMed PMID: 35106463; PubMed Central PMCID: PMC8786636.
Stoddard CI, Sung K, Ojee E, Adhiambo J, Begnel ER, Slyker J, Gantt S, Matsen FA 4th, Kinuthia J, Wamalwa D, Overbaugh J, Lehman DA. Distinct Antibody Responses to Endemic Coronaviruses Pre- and Post-SARS-CoV-2 Infection in Kenyan Infants and Mothers. Viruses. 2022 Jul 12;14(7). doi: 10.3390/v14071517. PubMed PMID: 35891497; PubMed Central PMCID: PMC9323260.
Slyker JA, Guthrie B, Pankau M, Tapia K, Wamalwa D, Benki-Nugent S, Ngugi E, Huang ML, Njuguna I, Langat A, John-Stewart G, Lehman D. Association Between Cytomegalovirus and Epstein-Barr Virus Viremia And Human Immunodeficiency Virus DNA Levels in the Reservoir of Kenyan Infants Receiving Antiretroviral Therapy. J Infect Dis. 2021 Jun 4;223(11):1923-1927. doi: 10.1093/infdis/jiaa640. PubMed PMID: 33064809; PubMed Central PMCID: PMC8176631.
Maqsood R, Reus JB, Wu LI, Holland LA, Nduati R, Mbori-Ngacha D, Maleche-Obimbo E, Begnel ER, Gantt S, Ojee E, Wamalwa D, John-Stewart G, Slyker J, Lehman DA, Lim ES. Breast Milk Virome and Bacterial Microbiome Resilience in Kenyan Women Living with HIV. mSystems. 2021 Mar 16;6(2). doi: 10.1128/mSystems.01079-20. PubMed PMID: 33727396; PubMed Central PMCID: PMC8546991.
Pankau MD, Reeves DB, Harkins E, Ronen K, Jaoko W, Mandaliya K, Graham SM, McClelland RS, Matsen Iv FA, Schiffer JT, Overbaugh J, Lehman DA. Dynamics of HIV DNA reservoir seeding in a cohort of superinfected Kenyan women. PLoS Pathog. 2020 Feb;16(2):e1008286. doi: 10.1371/journal.ppat.1008286. eCollection 2020 Feb. PubMed PMID: 32023326; PubMed Central PMCID: PMC7028291.
Pankau MD, Wamalwa D, Benki-Nugent S, Tapia K, Ngugi E, Langat A, Otieno V, Moraa H, Maleche-Obimbo E, Overbaugh J, John-Stewart GC, Lehman DA. Decay of HIV DNA in the Reservoir and the Impact of Short Treatment Interruption in Kenyan Infants. Open forum infectious diseases. 2018; 5(1):ofx268. PubMed [journal] PMID: 29354661, PMCID: PMC5767951
Slyker JA, Richardson B, Chung MH, Atkinson C, Ásbjörnsdóttir KH, Lehman DA, Boeckh M, Emery V, Kiarie J, John-Stewart G. Maternal Highly Active Antiretroviral Therapy Reduces Vertical Cytomegalovirus Transmission But Does Not Reduce Breast Milk Cytomegalovirus Levels. AIDS research and human retroviruses. 2017; 33(4):332-338. PubMed [journal] PMID: 27796131, PMCID: PMC5372773
Lillis L, Lehman DA, Siverson JB, Weis J, Cantera J, Parker M, Piepenburg O, Overbaugh J, Boyle DS. Cross-subtype detection of HIV-1 using reverse transcription and recombinase polymerase amplification. Journal of virological methods. 2016; 230:28-35. NIHMSID: NIHMS754843 PubMed [journal] PMID: 26821087, PMCID: PMC4767662
Weis JF, Baeten JM, McCoy CO, Warth C, Donnell D, Thomas KK, Hendrix CW, Marzinke MA, Mugo N, Matsen FA IV, Celum C, Lehman DA. Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation. AIDS (London, England). 2016; 30(1):31-5. NIHMSID: NIHMS728615 PubMed [journal] PMID: 26731753, PMCID: PMC4704103
Liu AY, Lohman-Payne B, Chung MH, Kiarie J, Kinuthia J, Slyker J, Richardson B, Lehman D, Farquhar C, John-Stewart G. Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya. Clinical and experimental immunology. 2015; 180(3):509-19. PubMed [journal] PMID: 25652232, PMCID: PMC4449779
Lehman DA, Baeten JM, McCoy CO, Weis JF, Peterson D, Mbara G, Donnell D, Thomas KK, Hendrix CW, Marzinke MA, Frenkel L, Ndase P, Mugo NR, Celum C, Overbaugh J, Matsen FA. Risk of drug resistance among persons acquiring HIV within a randomized clinical trial of single- or dual-agent preexposure prophylaxis. The Journal of infectious diseases. 2015; 211(8):1211-8. PubMed [journal] PMID: 25587020, PMCID: PMC4402339
Lehman DA, Ronen K, Blish CA, Baeten JM, Jalalian-Lechak Z, Jaoko W, Mandaliya K, Richardson BA, McClelland RS, Overbaugh J. Systemic cytokine levels show limited correlation with risk of HIV-1 acquisition. Journal of acquired immune deficiency syndromes (1999). 2014; 66(2):135-9. NIHMSID: NIHMS558609 PubMed [journal] PMID: 24413043, PMCID: PMC4020985
Boyle DS, Lehman DA, Lillis L, Peterson D, Singhal M, Armes N, Parker M, Piepenburg O, Overbaugh J. Rapid detection of HIV-1 proviral DNA for early infant diagnosis using recombinase polymerase amplification. mBio. 2013; 4(2). PubMed [journal] PMID: 23549916, PMCID: PMC3622927
Wamalwa DC, Lehman DA, Benki-Nugent S, Gasper MA, Gichohi R, Maleche-Obimbo E, Farquhar C, John-Stewart GC, Overbaugh J. Long-term virologic response and genotypic resistance mutations in HIV-1 infected Kenyan children on combination antiretroviral therapy. Journal of acquired immune deficiency syndromes (1999). 2013; 62(3):267-74. NIHMSID: NIHMS424677 PubMed [journal] PMID: 23196827, PMCID: PMC3593972
Lehman DA, Wamalwa DC, McCoy CO, Matsen FA, Langat A, Chohan BH, Benki-Nugent S, Custers-Allen R, Bushman FD, John-Stewart GC, Overbaugh J. Low-frequency nevirapine resistance at multiple sites may predict treatment failure in infants on nevirapine-based treatment. Journal of acquired immune deficiency syndromes (1999). 2012; 60(3):225-33. NIHMSID: NIHMS366134 PubMed [journal] PMID: 22395670, PMCID: PMC3383885
Slyker JA, Chung MH, Lehman DA, Kiarie J, Kinuthia J, Holte S, Tapia K, Njiri F, Overbaugh J, John-Stewart G. Incidence and correlates of HIV-1 RNA detection in the breast milk of women receiving HAART for the prevention of HIV-1 transmission. PloS one. 2012; 7(1):e29777. PubMed [journal] PMID: 22253778, PMCID: PMC3256181
Lehman DA, John-Stewart GC, Overbaugh J. Antiretroviral strategies to prevent mother-to-child transmission of HIV: striking a balance between efficacy, feasibility, and resistance. PLoS medicine. 2009; 6(10):e1000169. PubMed [journal] PMID: 19859532, PMCID: PMC2760781
Lehman DA, Chung MH, Mabuka JM, John-Stewart GC, Kiarie J, Kinuthia J, Overbaugh J. Lower risk of resistance after short-course HAART compared with zidovudine/single-dose nevirapine used for prevention of HIV-1 mother-to-child transmission. Journal of acquired immune deficiency syndromes (1999). 2009; 51(5):522-9. NIHMSID: NIHMS142011 PubMed [journal] PMID: 19502990, PMCID: PMC2765911
Lehman DA, Chung MH, John-Stewart GC, Richardson BA, Kiarie J, Kinuthia J, Overbaugh J. HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission. AIDS (London, England). 2008; 22(12):1475-85. NIHMSID: NIHMS142009 PubMed [journal] PMID: 18614871, PMCID: PMC2765916
Lehman DA, Farquhar C. Biological mechanisms of vertical human immunodeficiency virus (HIV-1) transmission. Reviews in medical virology. 2007; 17(6):381-403. PubMed [journal] PMID: 17542053