Eron J J, Vernazza P L, Johnston D M, Seillier-Moiseiwitsch F, Alcorn T M, Fiscus S A, Cohen M S
Department of Medicine, University of North Carolina at Chapel Hill, 27599-7030, USA.
AIDS. 1998 Oct 22;12(15):F181-9. doi: 10.1097/00002030-199815000-00003.
To evaluate blood and genital secretions from HIV-infected men for HIV-1 resistant to antiretroviral agents.
A longitudinal study of 11 men with HIV infection and persistent detectable HIV RNA levels in blood and semen on antiretroviral therapy.
HIV-1 from the blood and seminal plasma, obtained before the initiation of a new therapeutic regimen and on therapy, were evaluated by population-based sequencing of reverse transcriptase (RT) and protease RNA for the development of resistance to antiretroviral therapy. The genetic relatedness of sequences over time was compared.
RT genotypic resistance markers were present in seminal plasma at baseline in three out of six individuals with previous RT inhibitor experience. Eight out of 10 men, from whom the viral sequence was available on new therapy, demonstrated the evolution of new resistance mutations in the blood or seminal plasma, or both. The evolution of resistance mutations in blood and semen were frequently discordant, although over time similar patterns were seen. In two individuals, protease inhibitor resistance mutations evolved in the blood but not in the major variant in seminal plasma. Comparisons of the viral sequences between blood and seminal plasma from six men revealed two patterns. Three men showed a clustering of sequences from blood and semen. Three had sequences that appeared to evolve separately in the two compartments.
HIV-1 variants with genotypic resistance markers are present in the male genital tract and evolve over time on incompletely suppressive antiretroviral therapy. The absence of genotypic changes consistent with protease inhibitor resistance in the semen, despite their presence in blood plasma, suggests the possibility of limited penetration of these agents into the male genital tract. Sexual transmission of resistant variants may have a negative impact on treatment outcome in newly infected individuals and on the spread of the diseases within a population. Therapeutic strategies that fully suppress HIV-1 in the genital tract should be a public health priority.
评估感染HIV的男性血液和生殖分泌物中对抗逆转录病毒药物耐药的HIV-1。
一项针对11名感染HIV且在接受抗逆转录病毒治疗时血液和精液中持续可检测到HIV RNA水平的男性的纵向研究。
通过对逆转录酶（RT）和蛋白酶RNA进行基于群体的测序，评估在开始新治疗方案之前及治疗期间采集的血液和精液中的HIV-1，以了解对抗逆转录病毒治疗耐药性的发展情况。比较不同时间序列的遗传相关性。
在6名曾使用过RT抑制剂的个体中，有3人在基线时精液中存在RT基因型耐药标志物。在新治疗时可获得病毒序列的10名男性中，有8人在血液或精液或两者中出现了新的耐药突变演变。血液和精液中耐药突变的演变通常不一致，不过随着时间推移会出现相似模式。在2名个体中，蛋白酶抑制剂耐药突变在血液中出现，但精液中的主要变体中未出现。对6名男性血液和精液中的病毒序列进行比较发现了两种模式。3名男性血液和精液中的序列聚集在一起。另外3名男性的序列在两个隔室中似乎是分别演变的。
具有基因型耐药标志物的HIV-1变体存在于男性生殖道中，并在不完全抑制性的抗逆转录病毒治疗过程中随时间演变。尽管血浆中存在蛋白酶抑制剂耐药相关的基因型变化，但精液中未出现，这表明这些药物进入男性生殖道的穿透性可能有限。耐药变体的性传播可能会对新感染个体的治疗结果以及疾病在人群中的传播产生负面影响。在生殖道中完全抑制HIV-1的治疗策略应成为公共卫生的优先事项。
