BACKGROUND: The HIV reservoir largely consists of “defective” virus. Several studies now suggest that HIV+ cells harboring “intact” (i.e., potentially replication-competent) provirus decay faster than defective provirus during long-term antiretroviral therapy (ART) suppression. However, there are limited data describing HIV reservoir decay rates during the first few months of treated acute HIV.
METHODS: Individuals diagnosed with acute (<100 days) HIV were enrolled in the UCSF Treat Acute HIV study between 2015-2020. Participants were initiated on ART (tenofovir/emtricitabine+dolutegravir) and followed for 24+ weeks. Frequencies of intact vs. defective provirus were quantified using the intact proviral DNA assay (IPDA). Multivariate nonlinear general additive models included covariates for timing of ART initiation, initial CD4+ count, and pre-ART HIV RNA.
RESULTS: A total of 67 (83% of screened) participants were enrolled. The proportions of Fiebig I, II, III, IV, V disease were 12%, 15%, 8%, 17%, and 48%. Median age was 30. The cohort was 98% male; 15% African-American, 30% Latino, 21% Asian, 33% Caucasian. Higher initial CD4+ T cell count (Figure 1a) and lower pre-ART plasma HIV RNA (Figure 1b) predicted more rapid decay of defective and intact HIV DNA. Plasma HIV RNA declined to <40 copies/mL after a median of 31 days of ART. Both intact and defective provirus decayed rapidly in the first 50 days (3.6% vs. 4.3%), followed by a slower decay after 50 days (1.1% vs. 1.8%). Earlier ART initiation (Fiebig I-III) was associated with steeper declines in both intact and defective HIV DNA (Figure 1c). For each day delay in ART initiation, intact and defective HIV DNA decreased by 0.02% vs. 0.03% in the first 50 days and by 0.006% vs. 0.01% after 50 days of ART suppression.
CONCLUSIONS: We observed a two-phase decay of intact and defective HIV DNA that was significantly faster for individuals with earlier ART initiation. Decay rates were accelerated with earlier ART initiation. These findings may reflect virologic (rapid decay after plasma viremia suppression) and/or immunologic (contraction of activated cells to memory cells) phenomena in individuals with very small reservoirs and relatively intact immune responses, which can be leveraged in future cure strategies.