Alan Landay1, Elizabeth T Golub, Seema Desai, Jinbing Zhang, Val Winkelman, Kathryn Anastos, Helen Durkin, Mary Young, Maria C Villacres, Ruth M Greenblatt, Philip J Norris, Michael P Busch. 1. aDepartment of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois bDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland cResearch and Development Support Creative Testing Solutions, Tempe, Arizona dMontefiore Medical Center and Albert Einstein College of Medicine, Bronx eCenter for Allergy and Asthma Research, SUNY Downstate Medical Center, New York, New York fDivision of Infectious Disease, Georgetown University, Washington, DC gDepartment of Pediatrics and Molecular Microbiology and Immunology, University of Southern California, Los Angeles hDepartment of Clinical Pharmacy, Medicine, Epidemiology and Biostatistics iDepartment of Laboratory Medicine, Blood Systems Research Institute, University of California San Francisco, San Francisco, California, USA.
Abstract
OBJECTIVES: The introduction of HAART leads to control of HIV replication to less than 50 copies/ml, similar to levels in 'elite controllers'. Low-level viral replication may be one of the contributing factors to persistent immune activation/inflammation in HAART-treated individuals. There are still gaps in our knowledge of whether low-level replication persists in systemic versus mucosal sites. DESIGN AND METHODS: Participants for this study were recruited from the Women's Interagency HIV Study. We evaluated 33 'elite controllers' who naturally controlled HIV replication and 33 matched HAART-suppressed recipients. This study employed a sensitive target-capture transcription-mediated-amplification assay to compare low-level virus concentrations in plasma and cervical-vaginal lavage (CVL) samples from HIV-positive HAART recipients and 'elite controllers'. RESULTS: The median (interquartile range) plasma viral load signal/cut-off (S/Co) for 'elite controllers' was 10.5 (3.9-21.1), which was significantly (P < 0.001) higher than the S/Co for HAART recipients [2.0 (1-4.9)]. The majority of CVL samples from both groups had undetectable HIV RNA and the proportion of CVL samples with a cut-off more than 1.0 was not different between 'elite controllers' and HAART-suppressed recipients. CONCLUSION: This study demonstrated persistent low-level HIV replication in 'elite controllers', suggesting potential value of HAART treatment for these individuals. Absent or very low levels of HIV RNA in CVL indicate very low risk of secondary sexual transmission for both groups.
OBJECTIVES: The introduction of HAART leads to control of HIV replication to less than 50 copies/ml, similar to levels in 'elite controllers'. Low-level viral replication may be one of the contributing factors to persistent immune activation/inflammation in HAART-treated individuals. There are still gaps in our knowledge of whether low-level replication persists in systemic versus mucosal sites. DESIGN AND METHODS: Participants for this study were recruited from the Women's Interagency HIV Study. We evaluated 33 'elite controllers' who naturally controlled HIV replication and 33 matched HAART-suppressed recipients. This study employed a sensitive target-capture transcription-mediated-amplification assay to compare low-level virus concentrations in plasma and cervical-vaginal lavage (CVL) samples from HIV-positive HAART recipients and 'elite controllers'. RESULTS: The median (interquartile range) plasma viral load signal/cut-off (S/Co) for 'elite controllers' was 10.5 (3.9-21.1), which was significantly (P < 0.001) higher than the S/Co for HAART recipients [2.0 (1-4.9)]. The majority of CVL samples from both groups had undetectable HIV RNA and the proportion of CVL samples with a cut-off more than 1.0 was not different between 'elite controllers' and HAART-suppressed recipients. CONCLUSION: This study demonstrated persistent low-level HIV replication in 'elite controllers', suggesting potential value of HAART treatment for these individuals. Absent or very low levels of HIV RNA in CVL indicate very low risk of secondary sexual transmission for both groups.
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