AIDS THERAPIES IN ANIMAL RETROVIRUS MODELS

30例患者开始28天疗程的疗效观察 Mg/kg(R)-9-(2-膦甲氧基丙基)腺嘌呤(PMPA) 比较静脉接种SIV/DeltaB670的次数。 25只恒河猴每只静脉接种10只 100%感染剂量的SIV。每组5只猴子收到了 皮下治疗后，分别为1)28天 接种后24小时开始注射生理盐水；2)28天 PMPA启动24小时PI；3)PMPA启动28天；7天PI；4) 28天PMPA启动14天PI；或5)PMPA启动14天PI 并持续4个月。在生理盐水处理的对照组中，发病 血清p27抗原血症发生在第7-14天，并下降到 21-35天PI检测不到水平；抗原血症复发 早在70天前就被检测到；前病毒DNA变得持久 用聚合酶链式反应在PBMC中检测到7-14天PI；血浆病毒RNA 定量竞争聚合酶链式反应检测逆转录DNA (RT-QC-PCR)在4/5的对照组中持续7天PI，在所有对照组中处于水平 在14天内达到每毫升105至107个拷贝。开始PMPA治疗 24小时PI有很强的抗病毒作用 猴子出现血清抗原血症或可检测到的前病毒DNA PBMC在28天的治疗期间。然而，3/5的人接受了治疗 猴子在第42、84和119天成为P27和/或PCR阳性， ；治疗显然阻止了建立 2/5只猴子感染，治疗开始24小时PI。 开始治疗7天后，PI也有很强的抗病毒作用 抗原血症降低，前病毒DNA不太稳定 与对照组相比，血浆病毒RNA至少有所下降 在所有5只猴子中有1-2个对数，在2/5只猴子中达到无法检测到的水平。 开始治疗14天PI的早期效果较差，但 持续治疗导致病毒负担低于 对照组，血浆病毒RNA至少下降1-2个对数并下降 在2/5的猴子中低于可检测的限值。这些结果表明 PMPA在体内具有较强的抗SIV/DeltaB670的效力 其他人对SIVmne和SIVmac251的表现也是如此。

The effects of initiating 28 day periods of treatment with 30 mg/kg (R)-9-(2-phosphonylmethoxypropyl) adenine (PMPA) at different times after intravenous inoculation with SIV/DeltaB670 were compared. Twenty-five rhesus monkeys were each inoculated intravenously with 10 100% infectious doses of SIV. Groups of 5 monkeys each received the following subcutaneous treatments, respectively 1) 28 days of physiological saline initiated 24 hr postinoculation (PI); 2) 28 days of PMPA initiated 24 hr PI; 3) 28 days of PMPA initiated 7 days PI; 4) 28 days of PMPA initiated 14 days PI; or 5) PMPA initiated 14 days PI and continued for 4 months. In the saline-treated controls, the onset of serum p27 antigenemia occurred 7-14 days PI and declined to undetectable levels by 21-35 days PI; antigenemia recurrences were detected as early as 70 days PI; proviral DNA became persistently detectable by PCR in PBMC by 7-14 days PI; plasma viral RNA was detected by quantitative competitive PCR of reverse-transcribed DNA (RT-QC-PCR) in 4/5 controls by 7 days PI and in all controls at levels of 105 to 107 copies per ml by 14 days. Initiation of PMPA treatment 24 hr PI had a very potent antiviral effect none of the treated monkeys developed serum antigenemia or detectable proviral DNA in PBMCs during the 28 day treatment period. However, 3/5 treated monkeys became P27 and/or PCR positive on days 42, 84, and 119, respectively; treatment apparently prevented the establishment of infection in 2/5 monkeys in which treatment was initiated 24 hr PI. Initiation of treatment 7 days PI also had a strong antiviral effect antigenemia was decreased and proviral DNA was less consistently detected compared to controls; plasma viral RNA was decreased at least 1-2 logs in all 5 monkeys and to undetectable levels in 2/5 monkeys. Initiation of treatment 14 days PI had less early effect, but continuation of treatment resulted in lower virus burden compared to controls, decreasing plasma viral RNA at least 1-2 logs and falling below detectable limits in 2/5 monkeys. These results demonstrate that PMPA has strong potency against SIV/DeltaB670 in vivo similar to that shown by others for SIVmne and SIVmac251.