Evidence of persistent low-level viremia in long-term HAART-suppressed, HIV-infected individuals.
BACKGROUND
HAART can effectively reduce plasma HIV RNA levels to below the level of detection in most HIV-infected patients. The degree to which residual low-level viremia persists during HAART remains unclear.


METHODS
We identified 180 individuals (median duration of HIV infection 12 years) who had at least two consecutive plasma HIV-1 RNA levels below the level of detection (<50-75 copies/ml) while taking antiretroviral drugs; 36 of 180 had been virologically suppressed for more than 5 years. Longitudinal plasma samples that were taken from these individuals during periods of viral load suppression were selected and analyzed. The isothermal transcription-mediated amplification (TMA) (limit of detection <3.5 copies RNA/ml) assay was used to measure persistent viremia. A 'detuned' EIA assay was used to obtain quantitative HIV antibody levels.


RESULTS
A total of 1606 TMA assays were performed on 438 specimens in 180 HAART-suppressed individuals (median 3 replicates per specimen). In the first year of viral suppression, plasma RNA levels declined significantly (P = 0.001), but after month 12 there was no evidence for a continued decline (P = 0.383). In the first year of viral suppression, HIV antibody levels also declined (P = 0.054), but after month 12 there was no evidence for a continued decline (P = 0.988).


CONCLUSIONS
Viremia continued to decline during the first 12 months after viremia became undetectable using conventional methods, and then remained stable. HIV antibody levels also decreased in the first year of viral suppression and then remained stable. Viremia and the HIV-associated host response appear to achieve a steady-state 'set-point' during long-term combination therapy.
Hatano
Hiroyu
H
Department of Medicine, University of California,San Francisco, California, USA. hhatano@php.ucsf.edu
Delwart
Eric L
EL
Norris
Philip J
PJ
Lee
Tzong-Hae
TH
Neilands
Torsten B
TB
Kelley
Colleen F
CF
Hunt
Peter W
PW
Hoh
Rebecca
R
Linnen
Jeffrey M
JM
Martin
Jeffrey N
JN
Busch
Michael P
MP
Deeks
Steven G
SG
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000276:immunology*; D019562:Viral Load / Q000276:immunology*; D014766:Viremia / Q000276:immunology*
D015483:HIV Antibodies; D012367:RNA, Viral