Zhang H, Dornadula G, Beumont M, Livornese L, Van Uitert B, Henning K, Pomerantz R J
Center for Human Virology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
N Engl J Med. 1998 Dec 17;339(25):1803-9. doi: 10.1056/NEJM199812173392502.
Highly active antiretroviral therapy can effectively decrease the levels of human immunodeficiency virus type 1 (HIV-1) virions in peripheral plasma and seminal fluid of infected men. Whether the genital tract of HIV-1-infected men who are receiving highly active antiretroviral therapy and who have no detectable virus in the peripheral plasma harbors replication-competent virus is not known.
We collected peripheral-blood and semen samples from seven men with HIV-1 infections who were receiving highly active antiretroviral therapy and who had no detectable viral RNA (fewer than 50 copies per milliliter) in plasma and analyzed the samples for cell-associated proviral DNA using a quantitative polymerase-chain-reaction assay. Replication-competent viruses were evaluated by cell-coculture assays. Proviral DNA and replication-competent virus obtained from peripheral-blood and seminal cells were also analyzed by sequencing relevant viral genes.
Despite the long-term suppression of HIV-1 RNA in the plasma of the seven men, proviral DNA was detected in seminal cells in four. Replication-competent viruses were recovered from peripheral-blood cells in three men and from the seminal cells in two of these three men. The viruses recovered from the seminal cells had no genotypic mutations suggestive of resistance to antiretroviral drugs and were macrophage-tropic, a feature that is characteristic of HIV-1 strains that are capable of being sexually transmitted.
In HIV-1-infected men who are receiving highly active antiretroviral therapy and who have no detectable levels of viral RNA in plasma the virus may be present in seminal cells and therefore may be capable of being transmitted sexually.
高效抗逆转录病毒疗法可有效降低感染男性外周血浆和精液中1型人类免疫缺陷病毒(HIV-1)病毒粒子的水平。接受高效抗逆转录病毒疗法且外周血浆中未检测到病毒的HIV-1感染男性的生殖道是否存在具有复制能力的病毒尚不清楚。
我们收集了7名接受高效抗逆转录病毒疗法的HIV-1感染男性的外周血和精液样本,这些男性血浆中未检测到病毒RNA(每毫升少于50拷贝),并使用定量聚合酶链反应分析法分析样本中的细胞相关前病毒DNA。通过细胞共培养试验评估具有复制能力的病毒。还通过对相关病毒基因进行测序,分析从外周血和精细胞中获得的前病毒DNA和具有复制能力的病毒。
尽管这7名男性血浆中的HIV-1 RNA长期受到抑制,但在4人的精细胞中检测到了前病毒DNA。从3名男性的外周血细胞中以及这3名男性中的2人的精细胞中分离出了具有复制能力的病毒。从精细胞中分离出的病毒没有提示对抗逆转录病毒药物耐药的基因型突变,并且是嗜巨噬细胞型,这是能够性传播的HIV-1毒株的一个特征。
在接受高效抗逆转录病毒疗法且血浆中未检测到病毒RNA水平的HIV-1感染男性中,病毒可能存在于精细胞中,因此可能具有性传播能力。