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.

Automated summary

In people with HIV and viral suppression by antiretroviral therapy, the levels of intact proviral DNA initially decrease rapidly, but then slow down and may even increase over time. Different patterns of intact proviral DNA decay were observed, with some individuals experiencing a slower decline or even an increase in levels. The levels of defective proviral DNA remained stable. Mechanisms such as the persistence of cells with silent proviruses and the expansion of cells with intact proviruses may contribute to the slowing or reversal of the decay of intact proviral DNA.