Kantor, RamiBettendorf, DanielBosch, RonaldMann, MaritaKatzenstein, DavidCu-Uvin, SusanD’Aquila, RichardFrenkel, LisaFiscus, SusanCoombs, Robert2014-05-062014Kantor, Rami, Daniel Bettendorf, Ronald J. Bosch, Marita Mann, David Katzenstein, Susan Cu-Uvin, Richard D’Aquila, Lisa Frenkel, Susan Fiscus, and Robert Coombs. 2014. “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.” PLoS ONE 9 (4): e93537. doi:10.1371/journal.pone.0093537. http://dx.doi.org/10.1371/journal.pone.0093537.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152878Background: 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. Trial Registration ClinicalTrials.gov NCT00007488en-USBiology and life sciencesImmunologyClinical immunologyHIV immunopathogenesisMicrobiologyMedical MicrobiologyMicrobial PathogensViral PathogensImmunodeficiency VirusesHIVVirologyMedicine and health sciencesDiagnostic medicineHIV clinical manifestationsHIV diagnosis and managementEpidemiologyHIV epidemiologyInfectious DiseasesViral DiseasesPathology and Laboratory MedicineClinical PathologyClinical MicrobiologyPublic and occupational healthPreventive medicineHIV preventionJournal Article2014-05-0610.1371/journal.pone.0093537