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Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption


von Wyl, V; Gianella, S; Fischer, M; Niederoest, B; Kuster, H; Battegay, M; Bernasconi, E; Cavassini, M; Rauch, A; Hirschel, B; Vernazza, P; Weber, R; Joos, B; Günthard, H F (2011). Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption. PLoS ONE, 6(11):e27463.

Abstract

BACKGROUND:
Long-term benefits of combination antiretroviral therapy (cART) initiation during primary HIV-1 infection are debated.
METHODS:
The evolution of plasma HIV-RNA (432 measurements) and cell-associated HIV-DNA (325 measurements) after cessation of cART (median exposure 18 months) was described for 33 participants from the Zurich Primary HIV Infection Study using linear regression and compared with 545 measurements from 79 untreated controls with clinically diagnosed primary HIV infection, respectively a known date for seroconversion.
RESULTS:
On average, early treated individuals were followed for 37 months (median) after cART cessation; controls had 34 months of pre-cART follow-up. HIV-RNA levels one year after cART interruption were -0.8 log₁₀ copies/mL [95% confidence interval -1.2;-0.4] lower in early treated patients compared with controls, but this difference was no longer statistically significant by year three of follow-up (-0.3 [-0.9; 0.3]). Mean HIV-DNA levels rebounded from 2 log₁₀ copies [1.8; 2.3] on cART to a stable plateau of 2.7 log₁₀ copies [2.5; 3.0] attained 1 year after therapy stop, which was not significantly different from cross-sectional measurements of 9 untreated members of the control group (2.8 log₁₀ copies [2.5; 3.1]).
CONCLUSIONS:
The rebound dynamics of viral markers after therapy cessation suggest that early cART may indeed limit reservoir size of latently infected cells, but that much of the initial benefits are only transient. Owing to the non-randomized study design the observed treatment effects must be interpreted with caution.

BACKGROUND:
Long-term benefits of combination antiretroviral therapy (cART) initiation during primary HIV-1 infection are debated.
METHODS:
The evolution of plasma HIV-RNA (432 measurements) and cell-associated HIV-DNA (325 measurements) after cessation of cART (median exposure 18 months) was described for 33 participants from the Zurich Primary HIV Infection Study using linear regression and compared with 545 measurements from 79 untreated controls with clinically diagnosed primary HIV infection, respectively a known date for seroconversion.
RESULTS:
On average, early treated individuals were followed for 37 months (median) after cART cessation; controls had 34 months of pre-cART follow-up. HIV-RNA levels one year after cART interruption were -0.8 log₁₀ copies/mL [95% confidence interval -1.2;-0.4] lower in early treated patients compared with controls, but this difference was no longer statistically significant by year three of follow-up (-0.3 [-0.9; 0.3]). Mean HIV-DNA levels rebounded from 2 log₁₀ copies [1.8; 2.3] on cART to a stable plateau of 2.7 log₁₀ copies [2.5; 3.0] attained 1 year after therapy stop, which was not significantly different from cross-sectional measurements of 9 untreated members of the control group (2.8 log₁₀ copies [2.5; 3.1]).
CONCLUSIONS:
The rebound dynamics of viral markers after therapy cessation suggest that early cART may indeed limit reservoir size of latently infected cells, but that much of the initial benefits are only transient. Owing to the non-randomized study design the observed treatment effects must be interpreted with caution.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:21 Jan 2012 10:30
Last Modified:04 Jul 2016 14:24
Publisher:Public Library of Science (PLoS)
ISSN:1932-6203
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1371/journal.pone.0027463
PubMed ID:22102898
Permanent URL: http://doi.org/10.5167/uzh-55494

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