Simonetti Francesco R, Kearney Mary F
aHIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland, USA bDepartment of Biomedical and Clinical Sciences, L. Sacco, Milan, Italy.
Curr Opin HIV AIDS. 2015 Jan;10(1):49-54. doi: 10.1097/COH.0000000000000120.
HIV genetic diversity poses major challenges for the prevention, control, and cure of infection. Characterizing the diversity and evolution of HIV populations within the host provides insights into the mechanisms of HIV persistence during antiretroviral therapy (ART). This review describes the HIV diversity within patients, how it is affected by suppressive ART, and makes a case for early treatment after HIV infection.
HIV evolution is effectively halted by ART. However, cells that were infected prior to initiating therapy can proliferate to very high numbers both before and during treatment. Such clonal expansions result in the persistence of integrated proviruses despite therapy. These expanding proviruses have been shown to be a source for residual viremia during ART, and they may be a source for viral rebound after interrupting ART.
Plasma HIV RNA shows no evidence for evolution during ART, suggesting that HIV persistence is not driven by low-level, ongoing replication. The emergence of identical viral sequences observed in both HIV RNA and DNA is likely due to proliferation of infected cells. Early treatment restricts the viral population and reduces the number of variants that must be targeted for future therapeutic strategies.
HIV基因多样性给感染的预防、控制和治愈带来了重大挑战。了解宿主内HIV群体的多样性和进化有助于深入了解抗逆转录病毒疗法(ART)期间HIV持续存在的机制。本综述描述了患者体内的HIV多样性、其如何受到抑制性ART的影响,并论证了HIV感染后早期治疗的必要性。
ART可有效阻止HIV进化。然而,在开始治疗前已被感染的细胞在治疗前及治疗期间均可大量增殖。这种克隆性扩增导致整合的前病毒尽管接受治疗仍持续存在。这些不断扩增的前病毒已被证明是ART期间残余病毒血症的来源,并且可能是中断ART后病毒反弹的来源。
血浆HIV RNA在ART期间未显示出进化迹象,这表明HIV的持续存在并非由低水平的持续复制驱动。在HIV RNA和DNA中均观察到相同病毒序列的出现可能是由于受感染细胞的增殖。早期治疗可限制病毒群体并减少未来治疗策略必须针对的变异体数量。