Modifications of residual viraemia in human immunodeficiency virus-1-infected subjects undergoing repeated highly active antiretroviral therapy interruptions
Residual viraemia is detectable in the majority of human immunodeficiency virus (HIV)-infected subjects with plasma HIV-1 RNA <50 copies ml−1. In the present study, the impact of repeated treatment interruptions on residual HIV-1 viraemia was investigated in 58 subjects enrolled in the ISS-PART, a multicentre, randomized clinical trial comparing 24 months of continuous (arm A) and intermittent (arm B) highly active antiretroviral therapy (HAART). Residual viraemia was measured by a modified Roche Amplicor HIV-1 RNA assay (limit of detection 2.5 copies ml−1). At baseline, the median value of residual viraemia was 2.5 copies ml−1 in both arms; after 24 months, the median value was 2.5 in arm A and 8.3 in arm B. The median change from baseline to month 24 was significantly different between patients under continuous or intermittent HAART: 0 copies ml−1 (range −125.2 to +82.7) of HIV-1 RNA in arm A versus 2.1 copies ml−1 (range −80 to +46.8) in arm B (P=0.024). These results suggest that intermittent HAART tends to modify HIV-1 viraemia set point even if a virological response is achieved after HAART reinstitution.
FinziD.,
BlancksonJ.,
SilicianoJ. D.,
MargolickJ. B.,
ChadwickK.,
PiersonT.,
SmithK.,
LiszewiczJ.,
LoriF.other authors1999; Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 5:512–517[CrossRef]
FrostS. D. W.,
Martinez-PicadoJ.,
RuizL.,
ClotetB.,
BrownA. J.2002; Viral dynamics during structured treatment interruptions of chronic human immunodeficiency virus type 1 infection. J Virol 76:968–979[CrossRef]
HavlirD. V.,
StrainM. C.,
ClericiM.,
IgnacioC.,
TrabattoniD.,
FerranteP.,
WongJ. K.2003; Productive infection maintains a dynamic steady state of residual viremia in human immunodeficiency virus type-1 infected persons treated with suppressive antiretroviral therapy for five years. J Virol 77:11212–11219[CrossRef]
HavlirD. V.,
KoelschK. K.,
StrainM. C.,
MargotN.,
BiaoL.,
IgnacioC. C.,
MillerM. D.,
WongJ. K.2005; Predictors of residual viremia in HIV-infected patients successfully treated with efavirenz and lamivudine plus either tenofovir or stavudine. J Infect Dis 191:1164–1168[CrossRef]
MaldarelliF.,
PalmerS.,
KingM. S.,
WiegandA.,
PolisM. A.,
MicanJ.,
KovacsJ. A.,
DaveyR. T.,
Rock-KressD.other authors2007; ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog 3:e46[CrossRef]
McKinnonJ. E.,
ArribasJ. R.,
PulidoF.,
DelgadoR.,
MellorsJ. W.2006; The level of persistent HIV viremia does not increase after successful simplification of maintenance therapy to lopinavir/ritonavir alone. AIDS 20:2331–2335[CrossRef]
PalmerS.,
MaldarelliF.,
WiegandA.,
BernsteinB.,
HannaG. J.,
BrunS. C.,
KempfD. J.,
MellorsJ. W.,
CoffinJ. M.,
KingM. S.2008; Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A 105:3879–3884[CrossRef]
PalmisanoL.,
GiulianoM.,
NicastriE.,
PirilloM. F.,
AndreottiM.,
GalluzzoC. M.,
BucciardiniR.,
FragolaV.,
AndreoniM.,
VellaS.2005; Residual viremia in subjects with chronic HIV infection and viral load < 50 copies/ml: the impact of highly active antiretroviral therapy. AIDS 19:1843–1847[CrossRef]
Modifications of residual viraemia in human immunodeficiency virus-1-infected subjects undergoing repeated highly active antiretroviral therapy interruptions