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
Public Deposited- Creator
- Kantor, Rami
- Bettendorf, Daniel
- Bosch, Ronald J.
- Mann, Marita
- Katzenstein, David
- Cu-Uvin, Susan
- D’Aquila, Richard
- Frenkel, Lisa
- Fiscus, Susan
- Coombs, Robert
- Abstract
- BackgroundDetectable 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.MethodsBlood, 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.ResultsSamples 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.ConclusionsHIV 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 RegistrationClinicalTrials.gov NCT00007488
- Date of publication
- 2014
- Keyword
- Infectious Diseases
- Viral Pathogens
- Diagnostic medicine
- HIV diagnosis and management
- Microbial Pathogens
- Medicine and health sciences
- HIV clinical manifestations
- Viral Diseases
- Clinical Pathology
- Clinical Microbiology
- HIV immunopathogenesis
- Preventive medicine
- HIV epidemiology
- HIV
- Virology
- Public and occupational health
- Medical Microbiology
- Pathology and Laboratory Medicine
- Clinical immunology
- Immunodeficiency Viruses
- Immunology
- Epidemiology
- Microbiology
- Biology and life sciences
- DOI
- Identifier
- PMID: 24699474
- Onescience id: f6f79be37c425382194ccfbe913eaf505ec92f65
- PMCID: PMC3974754
- Publisher DOI: https://doi.org/10.1371/journal.pone.0093537
- Resource type
- Article
- Rights statement
- In Copyright
- Journal title
- PloS One
- Journal volume
- 9
- Journal issue
- 4
- Page start
- e93537
- Language
- English
- ISSN
- 1932-6203
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