Varied Patterns of Decay of Intact Human Immunodeficiency Virus Type 1 Proviruses Over 2 Decades of Antiretroviral Therapy

In people with Human Immunodeficiency Virus and viral suppression by antiretroviral therapy, intact proviral DNA levels initially decay rapidly, followed by a marked slowing of the decay and, in some individuals, a late increase in proviral DNA levels. Fourteen people with human immunodeficiency virus type 1 had longitudinal measurements of intact, defective, and total proviral DNA over the course of two decades of antiretroviral therapy. Three patterns of intact proviral DNA decay were revealed: (1) biphasic decline with markedly slower second-phase decline, (2) initial decline that transitions to a zero-slope plateau, and (3) initial decline followed by later increases in intact proviral DNA. Defective proviral DNA levels were essentially stable. Mechanisms of slowing or reversal of second-phase decay of intact proviral DNA may include the inability to clear cells with intact but transcriptionally silent proviruses and clonal expansion of cells with intact proviruses.