Guha Sujoy K
School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721 302, India.
Med Hypotheses. 2005;65(1):61-4. doi: 10.1016/j.mehy.2004.12.030.
HIV transmission from the male to the female is a major health problem. A hypothesis proposing an intra vas deferens implant of an antimicrobial compound to prevent the infection spread is presented. Mechanisms of action for the inhibition could include inactivating HIV in sperms passing through the vas deferens; drug release from the implant to destroy HIV entering into semen from genital structures distal to the vas deferens; and sperm acrosome released hyaluronidase mediated reabsorption of HIV. A subcomponent of the implant flowing along sperm pathway may have a role in reducing the entry of HIV from a positive female into penile tissue. A new drug RISUG (reversible inhibition of sperm under guidance) presently undergoing clinical trials for its contraceptive effect in the male (because it disrupts the sperm acrosome by an electrical charge and pH lowering effects) has also antimicrobial action. The drug being a combination of styrene maleic anhydride (SMA) and dimethyl sulfoxide (DMSO) on being injected into the lumen of the vas deferens produces styrene maleic acid thereby lowering pH; induces electrochemical action leading to a stable electrical charge generation; releases mandelic acid; and induces acrosome reaction in sperms with consequent release of hyaluronidase and sperm inactivation. Moreover, one time administration into the lumen of the vas gives long term action. All these phenomena very well match with the needs for HIV clearance of semen and hence RISUG is here proposed as a possible candidate material for the HIV inhibiting vas deferens implant when delivered in below contraceptive threshold dosage. For experimental validation, after obtaining data on the semen HIV load under control conditions in the HIV positive males inducted into the study, 30 mg of SMA in 120 microl of DMSO (contraceptive dose being 60 mg SMA+120 microl DMSO) is to be injected into vasa deferens bilaterally. Thereafter at intervals of one month the viral load needs to be determined in semen obtained either by masturbation or in lubricant free condom at intercourse - the method of collection remaining the same throughout for a particular subject. A significant reduction in the semen viral load following RISUG administration will validate the hypothesis. Speculated reduced female to male HIV transmission is more difficult to test. Nonspecific indications will come from a population study of the incidence of RISUG treated men becoming HIV positive as compared to that in the general population.
男性向女性传播艾滋病病毒是一个重大的健康问题。本文提出了一种通过在输精管内植入抗菌化合物来防止感染传播的假说。其抑制作用机制可能包括:使通过输精管的精子中的艾滋病病毒失活;植入物释放药物以破坏从输精管远端生殖结构进入精液的艾滋病病毒;精子顶体释放的透明质酸酶介导艾滋病病毒的重吸收。沿精子路径流动的植入物子成分可能在减少艾滋病病毒从阳性女性进入阴茎组织方面发挥作用。一种新药RISUG(引导下精子可逆抑制)目前正在进行男性避孕效果的临床试验(因为它通过电荷和降低pH值的作用破坏精子顶体),同时也具有抗菌作用。该药物是苯乙烯马来酸酐(SMA)和二甲基亚砜(DMSO)的组合,注入输精管腔后会产生苯乙烯马来酸,从而降低pH值;引发电化学作用导致产生稳定的电荷;释放扁桃酸;并诱导精子发生顶体反应,随后释放透明质酸酶并使精子失活。此外,一次性注入输精管腔可产生长期作用。所有这些现象都与清除精液中艾滋病病毒的需求非常吻合,因此,当以低于避孕阈值的剂量给药时,RISUG被提议作为一种可能的艾滋病病毒抑制输精管植入候选材料。为了进行实验验证,在纳入研究获得HIV阳性男性对照条件下精液HIV载量数据后,将30mg SMA溶于120微升DMSO中(避孕剂量为60mg SMA + 120微升DMSO)双侧注入输精管。此后,每隔一个月,需要通过手淫或在性交时使用无润滑剂避孕套获取精液来测定病毒载量——对于特定受试者,整个过程采集方法保持一致。RISUG给药后精液病毒载量显著降低将验证该假说。推测的女性向男性艾滋病病毒传播减少则更难测试。非特异性指标将来自对接受RISUG治疗的男性与普通人群中HIV阳性发生率的人群研究。