Kantor Rami, Bettendorf Daniel, Bosch Ronald J, Mann Marita, Katzenstein David, Cu-Uvin Susan, D'Aquila Richard, Frenkel Lisa, Fiscus Susan, Coombs Robert
Division of Infectious Diseases, Department of Medicine, Brown University Alpert Medical School, Providence, Rhode Island, United States of America.
Harvard School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
PLoS One. 2014 Apr 3;9(4):e93537. doi: 10.1371/journal.pone.0093537. eCollection 2014.
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.
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.
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.
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.
ClinicalTrials.gov NCT00007488.
体内各腔室中可检测到的HIV-1可导致传播及抗逆转录病毒耐药性。尽管已证实病毒脱落存在性别差异，但其机制和程度尚不清楚。在艾滋病临床试验组（ACTG）5077研究中，我们比较了开始/更换抗逆转录病毒治疗（ART）的男性和女性血液、生殖器分泌物及唾液中的RNA水平，以及血浆和生殖器分泌物中的耐药情况。
从美国14个地点的HIV感染成人（≥13岁）中收集血液、唾液和生殖器分泌物（腔室体液），这些成人开始或更换ART时血浆病毒载量（VL）≥2000拷贝/mL。对所有腔室体液进行VL检测，对血浆和生殖器分泌物进行HIV耐药基因分型。采用Spearman等级相关性评估一致性，采用Fisher精确检验和McNemar精确检验比较性别间及各腔室间的VL。
共获得143名受试者的样本；36%接受治疗（23名男性，29名女性），64%未治疗（40名男性，51名女性）。RNA检测在血浆中（100%）比在生殖器分泌物中（57%）和唾液中（64%）显著更频繁（P<0.001）。与女性相比，有生殖器脱落的男性比例更高（78%对41%），在校正检测限处的删失后，女性唾液中的RNA检测比生殖器分泌物中更频繁。两性的腔室间体液VL一致性均较低。在22对（13名男性，9名女性）来自接受治疗受试者的血浆-生殖器分泌物基因型中，大多数在血浆（77%）和生殖器分泌物（68%）中均有可检测到的耐药性。14%的受试者在各腔室间观察到耐药性不一致。
ACTG 5077受试者在开始/更换ART之前，HIV脱落和耐药性检测在组织间和性别间存在差异，使得金标准的血浆腔室评估不能完全代表其他组织部位的HIV情况。应进一步明确潜在的性别依赖性组织分隔机制，以帮助优化HIV治疗和预防传播。
ClinicalTrials.gov NCT00007488。
