HIV-1 RNA levels and antiretroviral drug resistance in blood and non-blood compartments from HIV-1-infected men and women enrolled in AIDS clinical trials group study A5077.
BACKGROUND
Detectable HIV-1 in body compartments can lead to transmission and antiretroviral resistance. Although sex differences in viral shedding have been demonstrated, mechanisms and magnitude are unclear. We compared RNA levels in blood, genital-secretions and saliva; and drug resistance in plasma and genital-secretions of men and women starting/changing antiretroviral therapy (ART) in the AIDS Clinical Trials Group (ACTG) 5077 study.


METHODS
Blood, saliva and genital-secretions (compartment fluids) were collected from HIV-infected adults (≥ 13 years) at 14 United-States sites, who were initiating or changing ART with plasma viral load (VL) ≥ 2,000 copies/mL. VL testing was performed on all compartment fluids and HIV resistance genotyping on plasma and genital-secretions. Spearman rank correlations were used to evaluate concordance and Fisher's and McNemar's exact tests to compare VL between sexes and among compartments.


RESULTS
Samples were available for 143 subjects; 36% treated (23 men, 29 women) and 64% 'untreated' (40 men, 51 women). RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001). A higher proportion of men had genital shedding versus women (78% versus 41%), and RNA detection was more frequent in saliva versus genital-secretions in women when adjusted for censoring at the limit of assay detection. Inter-compartment fluid VL concordance was low in both sexes. In 22 (13 men, 9 women) paired plasma-genital-secretion genotypes from treated subjects, most had detectable resistance in both plasma (77%) and genital-secretions (68%). Resistance discordance was observed between compartments in 14% of subjects.


CONCLUSIONS
HIV shedding and drug resistance detection prior to initiation/change of ART in ACTG 5077 subjects differed among tissues and between sexes, making the gold standard blood-plasma compartment assessment not fully representative of HIV at other tissue sites. Mechanisms of potential sex-dependent tissue compartmentalization should be further characterized to aid in optimizing treatment and prevention of HIV transmission.


BACKGROUND
ClinicalTrials.gov NCT00007488.
Division of Infectious Diseases, Department of Medicine, Brown University Alpert Medical School, Providence, Rhode Island, United States of America.
Rami
R
Kantor
Harvard School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Daniel
D
Bettendorf
Harvard School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
Ronald J
RJ
Bosch
Division of Infectious Diseases, Department of Medicine, Brown University Alpert Medical School, Providence, Rhode Island, United States of America.
Marita
M
Mann
Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California, United States of America.
David
D
Katzenstein
Division of Infectious Diseases, Department of Medicine, Brown University Alpert Medical School, Providence, Rhode Island, United States of America.
Susan
S
Cu-Uvin
Division of Infectious Diseases, Department of Medicine, Northwestern University, Chicago, Illinois, United States of America.
Richard
R
D'Aquila
Department of Pediatrics and Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
Lisa
L
Frenkel
Center for Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Susan
S
Fiscus
Department of Laboratory Medicine and Division of Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.
Robert
R
Coombs
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001769:Blood / Q000821:virology*; D001825:Body Fluid Compartments / Q000821:virology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D012463:Saliva / Q000821:virology; D019562:Viral Load / Q000235:genetics; D017201:Virus Shedding / Q000235:genetics
D019380:Anti-HIV Agents; D012367:RNA, Viral