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- Title
Intermittent HIV-1 Viremia (Blips) and Drug Resistance in Patients Receiving HAART.
- Authors
Nettles, Richard E.; Kieffer, Tara L.; Kwon, Patty; Monie, Daphne; Han, Yefei; Parsons, Teresa; Cofrancesco, Joseph; Gallant, Joel E.; Quinn, Thomas C.; Jackson, Brooks; Flexner, Charles; Carson, Kathryn; Ray, Stuart; Persaud, Deborah; Siliciano, Robert F.
- Abstract
Context Many patients infected with human immunodeficiency virus type 1 (HIV-1) and receiving highly active antiretroviral therapy experience intermittent episodes of detectable viremia (“blips”), which may raise concerns about drug resistance, lead to costly repeat measurements of viral RNA, and sometimes trigger alterations in therapy. Objective To test the hypothesis that blips represent random biological and statistical variation around mean steady-state HIV-1 RNA levels slightly below 50 copies/mL rather than biologically significant elevations in viremia. Design, Setting, and Patients Between June 19, 2003, and February 9, 2004, patients receiving therapy underwent intensive sampling (every 2-3 days) over 3 to 4 months to define the frequency, magnitude, and duration of blips and their association with drug levels and other clinical variables. Blips were defined as HIV-1 RNA measurements greater than or equal to 50 copies/mL preceded and followed by measurements less than 50 copies/mL without a change in treatment. To determine whether blips result from or lead to drug resistance, an ultrasensitive genotyping assay was used to detect drug resistance mutations before, during, and after blips. Patients were 10 HIV-1–infected asymptomatic adults recruited by clinicians and followed up in the Moore Clinic at the Johns Hopkins Hospital. Patients had suppression of viremia to below 50 copies/mL while receiving a stable antiretroviral regimen for 6 months or longer. Main Outcome Measures At each time point, plasma HIV-1 RNA levels were measured in 2 independent laboratories and drug resistance mutations were analyzed by clonal sequencing. Results With the intensive sampling, blips were detected in 9 of 10 patients. Statistical analysis was consistent with random assay variation around a mean viral load below 50 copies/mL. Blips were not concordant on independent testing and had a short duration (median, <3 days) and low magnitude (median, 7...
- Subjects
HIV-positive persons; ANTIVIRAL agents; DRUG resistance; MICROBIOLOGICAL assay; RNA; CLINICAL trials; HEALTH outcome assessment; DISEASES
- Publication
JAMA: Journal of the American Medical Association, 2005, Vol 293, Issue 7, p817
- ISSN
0098-7484
- Publication type
Article
- DOI
10.1001/jama.293.7.817