HIV-1 DNA decay dynamics in early treated individuals: practical considerations for clinical trial design

HIV-1 DNA decay dynamics in early treated individuals: practical considerations for clinical trial design

Fecha de publicación online: 17/04/2020 Fecha de publicación en papel: 17 Abril 2020 Revista: Journal of Antimicrobial Chemotherapy

Abstract:

Background
Initiation of combination antiretroviral therapy (cART) soon after HIV-1 infection limits the establishment of viral reservoirs. Thus, early treated individuals are preferred candidates to evaluate novel viral remission strategies. However, their cART-dependent HIV-1 DNA decay dynamics are still poorly defined. This can hamper the design and interpretation of results from clinical trials intended to further reduce viral reservoirs.

Objectives
To clarify the duration of cART needed for the HIV-1 reservoir to be stabilized in early treated individuals.

Methods
We characterized the longitudinal decline of total HIV-1 DNA levels by droplet digital PCR in 21 individuals initiating cART within 6 months after estimated HIV-1 acquisition. Measurements were taken at cART initiation, after 6 months and annually until Year 4. Correlations between virological and clinical parameters were statistically analysed. Statistical modelling was performed applying a mixed-effects model.

Results
Total HIV-1 DNA experienced a median overall decrease of 1.43 log10 units (IQR = 1.17–1.69) throughout the 4 years of follow-up. Baseline levels for total HIV-1 DNA, viral load, absolute CD4+ T cell count and CD4+/CD8+ ratio correlate with final HIV-1 DNA measurements (R2=0.68, P <0.001; R2=0.54, P =0.012; R2=−0.47, P =0.031; and R2=−0.59, P =0.0046, respectively). Statistical modelling shows that after 2 years on cART the viral reservoir had reached a set point.

Conclusions
A waiting period of 2 years on cART should be considered when designing interventions aiming to impact latent HIV-1 reservoir levels and viral rebound kinetics after cART discontinuation, in order to facilitate interpretation of results and enhance the chance of viral control.

Autores: Bayón-Gil A, Puertas MC, Urrea V, Bailón L, Morón-López S, Cobarsí P, Brander C, Mothe B, Martinez-Picado J

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