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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.

Kantor R, Bettendorf D, Bosch RJ, Mann M, Katzenstein D, Cu-Uvin S, D'Aquila R, Frenkel L, Fiscus S, Coombs R, ACTG A5077 Study Te - PLoS ONE (2014)

Bottom Line: RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001).Resistance discordance was observed between compartments in 14% of subjects.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Medicine, Brown University Alpert Medical School, Providence, Rhode Island, United States of America.

ABSTRACT

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.

Trial registration: ClinicalTrials.gov NCT00007488.

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Related in: MedlinePlus

Association of Blood-Plasma and Genital Tract Fluid HIV RNA by Sex.Scatterplots demonstrating the Spearman correlations between blood and seminal plasma (A) and between blood and SnoStrip (B) viral load. Filled symbols represent those with paired blood and genital secretion genotypes; individuals with detectable drug resistance mutations in either blood or genital secretions are marked with an ‘x’.
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pone-0093537-g003: Association of Blood-Plasma and Genital Tract Fluid HIV RNA by Sex.Scatterplots demonstrating the Spearman correlations between blood and seminal plasma (A) and between blood and SnoStrip (B) viral load. Filled symbols represent those with paired blood and genital secretion genotypes; individuals with detectable drug resistance mutations in either blood or genital secretions are marked with an ‘x’.

Mentions: Median plasma HIV RNA level in treated, ‘untreated’ and overall was 4.6, 4.8 and 4.7 log10 RNA copies/mL in men and 4.4, 4.8 and 4.7 log10 RNA copies/mL in women, respectively (p = 0.50 comparing all). Paired HIV RNA values were lower in all non-plasma compartments compared to plasma (Figure 2). Concordance of HIV RNA levels between blood plasma and genital-secretions was low and not significant in men (r = 0.26, 0.21 and 0.24 for treated, ‘untreated’ and overall; Figure 3a), and low but reaching statistical significance (p<0.05) for ‘untreated’ and overall in women (r = 0.20, 0.37 and 0.32 for treated, ‘untreated’ and overall; Figure 3b). For both men and women, detection of HIV RNA in genital fluids was infrequent when the plasma viral RNA level was <4.0 RNA log10 copies/mL.


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.

Kantor R, Bettendorf D, Bosch RJ, Mann M, Katzenstein D, Cu-Uvin S, D'Aquila R, Frenkel L, Fiscus S, Coombs R, ACTG A5077 Study Te - PLoS ONE (2014)

Association of Blood-Plasma and Genital Tract Fluid HIV RNA by Sex.Scatterplots demonstrating the Spearman correlations between blood and seminal plasma (A) and between blood and SnoStrip (B) viral load. Filled symbols represent those with paired blood and genital secretion genotypes; individuals with detectable drug resistance mutations in either blood or genital secretions are marked with an ‘x’.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3974754&req=5

pone-0093537-g003: Association of Blood-Plasma and Genital Tract Fluid HIV RNA by Sex.Scatterplots demonstrating the Spearman correlations between blood and seminal plasma (A) and between blood and SnoStrip (B) viral load. Filled symbols represent those with paired blood and genital secretion genotypes; individuals with detectable drug resistance mutations in either blood or genital secretions are marked with an ‘x’.
Mentions: Median plasma HIV RNA level in treated, ‘untreated’ and overall was 4.6, 4.8 and 4.7 log10 RNA copies/mL in men and 4.4, 4.8 and 4.7 log10 RNA copies/mL in women, respectively (p = 0.50 comparing all). Paired HIV RNA values were lower in all non-plasma compartments compared to plasma (Figure 2). Concordance of HIV RNA levels between blood plasma and genital-secretions was low and not significant in men (r = 0.26, 0.21 and 0.24 for treated, ‘untreated’ and overall; Figure 3a), and low but reaching statistical significance (p<0.05) for ‘untreated’ and overall in women (r = 0.20, 0.37 and 0.32 for treated, ‘untreated’ and overall; Figure 3b). For both men and women, detection of HIV RNA in genital fluids was infrequent when the plasma viral RNA level was <4.0 RNA log10 copies/mL.

Bottom Line: RNA detection was significantly more frequent in plasma (100%) than genital-secretions (57%) and saliva (64%) (P<0.001).Resistance discordance was observed between compartments in 14% of subjects.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Medicine, Brown University Alpert Medical School, Providence, Rhode Island, United States of America.

ABSTRACT

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.

Trial registration: ClinicalTrials.gov NCT00007488.

Show MeSH
Related in: MedlinePlus