Intact and Defective HIV Provirus Changes During Antiretroviral Therapy in People Treated during Acute or Chronic HIV Infection or as HIV Controllers

Abstract Background Intact proviral DNA (IPD) is a measure of the replication-competent HIV reservoir. Little is known about how IPD levels compare in people with HIV (PWH) who initiate antiretroviral therapy (ART) during acute HIV infection (AHI), chronic infection (CHI) or as HIV controllers (CON). Methods Participants with sustained plasma HIV RNA 50 copies/mL on ART had longitudinal measurements of intact, defective and total proviral DNA in blood samples. Results Twenty-nine participants were evaluated: 14 CHI, 7 AHI, 8 CON. PWH-CON had lower IPD than PWH-AHI or PWH-CHI during ART. PWH-CON also had low intact and total provirus levels before initiating ART. During years 2-5 of ART, IPD decay half-life was 1.0 years in PWH-AHI, 1.6 years in PWH-CHI and 3.2 years in PWH-CON (p=0.01 for PWH-CON versus PWH-AHI). Defective provirus levels did not decrease in PWH-AHI and PWH-CHI. Conclusion During the initial years of ART, PWH treated during acute and chronic infection have decay in intact but not defective proviruses. PWH controllers have low intact and total provirus levels before and during ART, suggesting interactions between host and virus shape the proviral landscape. Variable proviral decay patterns in these populations provide insight into approaches to achieve ART-free HIV remission.