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

Abstract

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.

Keywords: HIV; antiretroviral therapy; intact proviruses; reservoirs.

Figure 1.

Examples of decay patterns in intact proviral DNA (IPD) for participants on long-term antiretroviral therapy (ART). A, Five participants had a similar pattern with slowing decay of intact proviruses during the second decade of ART. B, Three participants showed plateauing of decay (second phase slope effectively zero). C, Two participants had patterns of late increases. Abbreviation: NA, not applicable.