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Evidence of persistent low-level viremia in long-term HAART-suppressed individuals
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Reported by Jules Levin
CROI 2009 Feb 8-12
Hiroyu Hatano1, Eric Delwart1,2, Philip J. Norris1,2, Tzong-Hae Lee2, Joan Dunn-Williams2, Peter Hunt1, Rebecca Hoh1,
Jeffrey N. Martin1, Michael P. Busch1,2, and Steven G. Deeks1
1University of California, San Francisco; 2Blood Systems Research Institute, San Francisco, C
Results
Ultra-sensitive Plasma HIV-1 RNA Levels
A total of 1606 TMA assays were performed on 438 specimens in 180 HAART-suppressed subjects (median 3 replicates per specimen). In the first year of viral suppression, plasma RNA levels declined at a rate of -0.25 S/Co per month (p=0.001), but after month 12 there was no evidence for a continued decline (p=0.383) (Figure 2).
HIV-1 antibody levels
A total of 189 LS-EIA's were performed on 98/180 HAART- suppressed subjects. In the first year of viral suppression, HIV antibody levels declined at a rate of - 0.10 SOD per month (p=0.054), but after month 12 there was no evidence for a continued decline (p=0.988) (Figure 3).
Author Conclusions
Residual viremia is commonly observed in long-term HAART-suppressed patients, and appears to remain stable after 1 year of viral load suppression
There is an initial decline in HIV antibody levels that occurs shortly after suppression of plasma viral load. HIV antibody levels subsequently stabilize during long-term HAART, suggesting a steady-state relationship between virus and the host.
ABSTRACT
Background: HAART can effectively reduce plasma HIV RNA levels to below the level of detection using conventional assays in most HIV-infected patients (<50 to 75 copies/mL). The degree to which residual low-level viremia persists during long-term HAART remains unclear, particularly as most studies using highly sensitive assays have had limited follow-up times.
Methods: The isothermal transcription-mediated amplification (TMA) (Aptima, Gen-Probe) assay was used to measure longitudinal plasma HIV RNA levels in 180 HAART-suppressed subjects from the SCOPE cohort. The sensitivity of the TMA assay is <3 RNA copies/mL when 4 replicates are performed. All TMA assays with a signal:cutoff (S/Co) ratio ³1 were considered positive. In addition, a "detuned" or less-sensitive enzyme immunoassay (LS-EIA) was used to obtain quantitative HIV antibody levels (measured as standardized optical density [SOD]) over time.
Results: The median pre-HAART CD4+ T cell nadir count was 100 cells/mm3. Median duration of HIV infection was 12 years. Median duration of suppressive HAART was 13 months (IQR 3.9 to 46 months); 36 subjects were suppressed for ³5 years. A total of 1606 TMA assays were performed on 438 specimens (median 3 replicates per specimen) from 180 HAART-suppressed subjects. A mixed effect linear model showed an average of 0.06 decrease in S/Co per month (p <0.001); however, there was no significant change in plasma viremia over time when the analysis was limited to subjects who had been suppressed for ³12 months (n = 92, average of 0.03 decrease in S/Co per month, p = 0.097) or ³60 months (n = 36, average of 0.10 decrease in S/Co per month, p = 0.445). The proportion of subjects with low-level detectable viremia after 1 year of viral load suppression was 76% to 87% and did not appear to change over 7 years of suppression. Similarly, a mixed effect linear model showed an average of 0.03 decrease in HIV antibody levels per month (p = 0.006); however, there was no significant change over time when the analysis was limited to subjects who had been suppressed for ³12 months (n = 34).
Conclusions: Residual viremia is commonly observed in long-term HAART-suppressed patients, and appears to remain stable after 1 year of viral load suppression. HIV antibody levels are also stable during long-term HAART, suggesting a steady-state relationship between virus and the host response.
Background
Highly active antiretroviral therapy (HAART) can effectively reduce plasma HIV RNA levels to below the level of detection using conventional assays in most HIV-infected patients (<50-75 copies/mL). The degree to which residual low-level viremia persists during long-term HAART remains unclear, particularly as most studies using highly sensitive assays have had limited follow-up times.
Methods
Study Participants
All subjects were enrolled in SCOPE, an ongoing prospective cohort study. All subjects in SCOPE are seen every four months, at which time they are interviewed and plasma and PBMCs are stored. From this cohort, we identified subjects who had at least 2 consecutive plasma HIV-1 RNA levels below the level of detection (<50-75 copies/mL) while taking antiretroviral drugs. Plasma samples from these subject that were taken during periods of viral load suppression (<50-75 copies/mL) were selected and analyzed.
Ultra-sensitive Plasma HIV-1 RNA (TMA) assay
The isothermal Transcription Mediated Amplification (TMA) (Aptima, Gen-Probe) assay was used to obtain longitudinal measurements of plasma HIV RNA. The TMA assay provides quantitative data regarding plasma HIV RNA levels (Hatano et al, JV 2009). The sensitivity of the assay is < 3 RNA copies/mL when 4 replicates are performed. All TMA assays with a signal:cutoff (S/Co) ratio ≥1 were considered "positive."
HIV-1 antibody assay (LS-EIA)
A "detuned" or less-sensitive EIA (LS-EIA) (Organon Tecnika Vironostik [OTV], BioMerieux) assay was used to obtain quantitative HIV antibody levels (measured as standardized optical density [SOD]) over time. The OTV is a second-generation ELISA that detects IgG and IgM antibodies to HIV-1; the less sensitive modification (LS-EIA) involves testing 1:20,000 dilutions of plasma under abbreviated incubation conditions.
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