Clarridge, Katherine E.Blazkova, JanaEinkauf, KevinPetrone, MaryRefsland, Eric W.Justement, J. ShawnShi, VictoriaHuiting, Erin D.Seamon, Catherine A.Lee, Guinevere Q.Yu, Xu G.Moir, SusanSneller, Michael C.Lichterfeld, MathiasChun, Tae-Wook2018-02-262018Clarridge, K. E., J. Blazkova, K. Einkauf, M. Petrone, E. W. Refsland, J. S. Justement, V. Shi, et al. 2018. “Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.” PLoS Pathogens 14 (1): e1006792. doi:10.1371/journal.ppat.1006792. http://dx.doi.org/10.1371/journal.ppat.1006792.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34868840Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals. Here, we show a significant increase of HIV burden in the CD4+ T cells of infected individuals during ATI that was correlated with the level of plasma viral rebound. However, the size of the HIV reservoirs as well as immune parameters, including markers of exhaustion and activation, returned to pre-ATI levels 6–12 months after the study participants resumed ART. Of note, the proportions of near full-length, genome-intact and structurally defective HIV proviral DNA sequences were similar prior to ATI and following reinitiation of ART. In addition, there was no evidence of emergence of antiretroviral drug resistance mutations within intact HIV proviral DNA sequences following reinitiation of ART. These data demonstrate that short-term ATI does not necessarily lead to expansion of the persistent HIV reservoir nor irreparable damages to the immune system in the peripheral blood, warranting the inclusion of ATI in future clinical trials evaluating curative strategies.en-USBiology and Life SciencesMicrobiologyMedical MicrobiologyMicrobial PathogensViral PathogensImmunodeficiency VirusesHIVMedicine and Health SciencesPathology and Laboratory MedicinePathogensOrganismsVirusesBiology and life sciencesRNA virusesRetrovirusesLentivirusCell BiologyCellular TypesAnimal CellsBlood CellsWhite Blood CellsT CellsImmune CellsImmunologyVaccination and ImmunizationAntiviral TherapyAntiretroviral TherapyPublic and Occupational HealthPreventive MedicineCell biologyCellular typesAnimal cellsBlood cellsWhite blood cellsT cellsCytotoxic T cellsImmune cellsMedicine and health sciencesDatabase and informatics methodsBioinformaticsSequence analysisDNA sequence analysisInfectious DiseasesViral DiseasesViremiaVirologyViral ReplicationAnatomyBody FluidsBloodBlood PlasmaPhysiologyJournal Article2018-02-2610.1371/journal.ppat.1006792