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Low-level HIV Persists Despite Long-term Suppressive Antiretroviral Therapy

People on long-term antiretroviral therapy (ART) reach an HIV viral load and antibody "set-point," with a low level of persistent virus detectable using sensitive tests, according to study findings reported in the October 23, 2010 issue of AIDS. This research adds to the evidence that ART alone is not sufficient to eradicate all HIV from the body.

The idea of a cure for HIV has gained traction among researchers over the past year, but so far studies have found that even the most intensive antiretroviral regimens cannot eliminate the virus.

Contributing to this evidence, Hiroyu Hatano and Steven Deeks from the University of California at San Francisco and colleagues looked at residual HIV levels and changes in antibody levels among participants in the SCOPE cohort, consisting of HV positive people on stable suppressive ART.

The analysis included 180 individuals with at least 2 consecutive plasma HIV-1 RNA levels below the limit of detection on standard tests (< 50-75 copies/mL) while taking antiretroviral drugs. Most (84%) were men, the median age was 46 years, and the median duration of HIV infection was 12 years. Some participants (20%) had suppressed viral load for more than 5 years.

Investigators used a sensitive HIV RNA testing technique known as isothermal transcription-mediated amplification (TMA), with a limit of detection of less than 3.5 copies/mL. A total of 1606 TMA assays were performed on 438 patient samples. They also used a detuned enzyme immunoassay (EIA) assay to more precisely measure HIV antibody levels.

Results

• During the first year of viral suppression, plasma RNA levels declined significantly.
• After 12 months, however, HIV RNA reached a stable level and there was no evidence of continued decline.
• During the first year of suppression, HIV antibody levels also declined.
• Again, after 12 months, no further reduction was observed.

Based on these findings the study authors concluded, "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," they continued. "Viremia and the HIV-associated host response appear to achieve a steady-state 'set-point' during long-term combination therapy."

"The observed initial decrease, then stability, of residual viremia may represent residual virus arising from different cellular compartments," they elaborated in their discussion. "The observed low-level viremia in these HAART-suppressed individuals may reflect ongoing viral replication or release of RNA from a long-lived latent reservoir (which can theoretically persist indefinitely in the absence of active viral turnover)."

While the source of residual viremia in people on ART remains the subject of ongoing debate, several studies have shown that intensification of therapy by adding more antiretroviral drugs does not eliminate all virus, lending support to the theory that low-level HIV continues to be released from "reservoirs" such as resting memory CD T-cells.

"[W]e did not observe a direct relationship between baseline plasma HIV RNA levels and baseline HIV antibody levels," the authors wrote, noting that this was contrary to findings in "elite controllers" who are able to maintain undetectable viral load without ART, who show a direct correlation between plasma HIV RNA and HIV antibody levels. "The lack of association in HAART-suppressed individuals may point to different mechanisms of viral control in these two patient populations," they suggested.

Investigator affiliations: Department of Medicine, University of California at San Francisco, San Francisco, CA; Blood Systems Research Institute; Department of Laboratory Medicine; Center for AIDS Prevention Studies, University of California at San Francisco, San Francisco, CA; Emory University, Atlanta, GA; Gen-Probe Inc., San Diego, CA.

12/10/10

Reference

H Hatano, EL Delwart, PJ Norris, S Deeks, and others. Evidence of persistent low-level viremia in long-term HAART-suppressed, HIV-infected individuals. AIDS 24(16): 2535-2539 (Abstract). October 23, 2010.