Header

UZH-Logo

Maintenance Infos

Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1


Strain, Matthew C; Little, Susan J; Daar, Eric S; Havlir, Diane V; Günthard, Huldrych F; Lam, Ruby Y; Daly, Otto A; Nguyen, Juin; Ignacio, Caroline C; Spina, Celsa A; Richman, Douglas D; Wong, Joseph K (2005). Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1. Journal of Infectious Diseases, 191(9):1410-1418.

Abstract

Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatment

Abstract

Patients in whom virologic suppression is achieved with highly active antiretroviral therapy (HAART) retain long-lived cellular reservoirs of human immunodeficiency virus type 1 (HIV-1); this retention is an obstacle to sustained control of infection. To assess the impact that initiating treatment during primary HIV-1 infection has on this cell population, we analyzed the decay kinetics of HIV-1 DNA and of infectivity associated with cells activated ex vivo in 27 patients who initiated therapy before or <6 months after seroconversion and in whom viremia was suppressed to <50 copies/mL. The clearance rates of cellular reservoirs could not be distinguished by these techniques (median half-life, 20 weeks) during the first year of HAART. The clearance of HIV-1 DNA slowed significantly during the subsequent 3 years of treatment (median half-life, 70 weeks), consistent with heterogeneous cellular reservoirs being present. Total cell-associated infectivity (CAI) after 1 year of treatment was undetectable (<0.07 infectious units/million cells [IUPM]) in most patients initiating treatment during primary infection either before (9/9) or <6 months after (6/8) seroconversion. In contrast, all 17 control patients who initiated HAART during chronic infection retained detectable CAI after 3-6 years of treatment (median reservoir size, 1.1 IUPM; P<.0005). These results suggest that treatment <6 months after seroconversion may facilitate long-term control of cellular reservoirs that maintain HIV-1 infection during treatment

Statistics

Citations

Dimensions.ai Metrics
213 citations in Web of Science®
204 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 17 Oct 2018
17 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 May 2005
Deposited On:17 Oct 2018 15:16
Last Modified:30 Oct 2018 19:49
Publisher:Oxford University Press
ISSN:0022-1899
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1086/428777
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101086428777 (Library Catalogue)
PubMed ID:15809898

Download

Download PDF  'Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1'.
Preview
Content: Published Version
Language: English
Filetype: PDF (Nationallizenz 142-005)
Size: 731kB
View at publisher