Landay Alan, Golub Elizabeth T, Desai Seema, Zhang Jinbing, Winkelman Val, Anastos Kathryn, Durkin Helen, Young Mary, Villacres Maria C, Greenblatt Ruth M, Norris Philip J, Busch Michael P
aDepartment of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois bDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland cResearch and Development Support Creative Testing Solutions, Tempe, Arizona dMontefiore Medical Center and Albert Einstein College of Medicine, Bronx eCenter for Allergy and Asthma Research, SUNY Downstate Medical Center, New York, New York fDivision of Infectious Disease, Georgetown University, Washington, DC gDepartment of Pediatrics and Molecular Microbiology and Immunology, University of Southern California, Los Angeles hDepartment of Clinical Pharmacy, Medicine, Epidemiology and Biostatistics iDepartment of Laboratory Medicine, Blood Systems Research Institute, University of California San Francisco, San Francisco, California, USA.
AIDS. 2014 Mar 13;28(5):739-43. doi: 10.1097/QAD.0000000000000150.
The introduction of HAART leads to control of HIV replication to less than 50 copies/ml, similar to levels in 'elite controllers'. Low-level viral replication may be one of the contributing factors to persistent immune activation/inflammation in HAART-treated individuals. There are still gaps in our knowledge of whether low-level replication persists in systemic versus mucosal sites.
Participants for this study were recruited from the Women's Interagency HIV Study. We evaluated 33 'elite controllers' who naturally controlled HIV replication and 33 matched HAART-suppressed recipients. This study employed a sensitive target-capture transcription-mediated-amplification assay to compare low-level virus concentrations in plasma and cervical-vaginal lavage (CVL) samples from HIV-positive HAART recipients and 'elite controllers'.
The median (interquartile range) plasma viral load signal/cut-off (S/Co) for 'elite controllers' was 10.5 (3.9-21.1), which was significantly (P < 0.001) higher than the S/Co for HAART recipients [2.0 (1-4.9)]. The majority of CVL samples from both groups had undetectable HIV RNA and the proportion of CVL samples with a cut-off more than 1.0 was not different between 'elite controllers' and HAART-suppressed recipients.
This study demonstrated persistent low-level HIV replication in 'elite controllers', suggesting potential value of HAART treatment for these individuals. Absent or very low levels of HIV RNA in CVL indicate very low risk of secondary sexual transmission for both groups.
高效抗逆转录病毒疗法(HAART)的引入可使HIV复制得到控制,病毒载量降至每毫升50拷贝以下,与“精英控制者”体内的水平相似。低水平病毒复制可能是接受HAART治疗的个体持续免疫激活/炎症的促成因素之一。在系统性与黏膜部位低水平复制是否持续存在方面,我们的认知仍存在差距。
本研究的参与者来自女性机构间HIV研究。我们评估了33名自然控制HIV复制的“精英控制者”以及33名匹配的接受HAART治疗且病毒得到抑制的受试者。本研究采用了一种灵敏的靶标捕获转录介导扩增检测法,比较HIV阳性的HAART治疗受试者和“精英控制者”血浆及宫颈阴道灌洗液(CVL)样本中的低水平病毒浓度。
“精英控制者”血浆病毒载量信号/临界值(S/Co)的中位数(四分位间距)为10.5(3.9 - 21.1),显著高于接受HAART治疗者的S/Co [2.0(1 - 4.9)](P < 0.001)。两组的大多数CVL样本中均未检测到HIV RNA,且“精英控制者”和接受HAART治疗且病毒得到抑制的受试者中,临界值大于1.0的CVL样本比例无差异。
本研究表明“精英控制者”存在持续性低水平HIV复制,提示HAART治疗对这些个体具有潜在价值。CVL中HIV RNA缺失或水平极低表明两组发生性传播感染的风险都非常低。