Efficacy and safety of two-drug regimens for treatment of HIV in the central nervous system.
Efficacy and safety of two-drug regimens for treatment of HIV in the central nervous system.
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DOI：
10.1097/qad.0000000000002665
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发表时间：
2020-11-01
期刊：
影响因子：
--
通讯作者：
Letendre SL
中科院分区：
文献类型：
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作者：
Gabuzda D;McArthur JC;Letendre SL
HIV can infect the central nervous system (CNS) soon after transmission, and early initiation of antiretroviral therapy (ART) reduces the establishment or persistence of viral reservoirs in the CNS compartment as well as HIV-associated CNS injury [1, 2]. Successful treatment and virus eradication will require approaches that are effective, well tolerated and durable in the CNS [3, 4]. Despite current ART regimens that suppress HIV RNA in blood to undetectable levels, people with HIV (PWH) differ substantially in HIV RNA concentrations in cerebrospinal fluid (CSF)[5–8]. In most PWH, HIV RNA concentrations in CSF are more than 1 log10 copies/ml lower in CSF than in blood. After initiation of ART, viral suppression in blood is the primary determinant of viral suppression in CSF [5, 7]. During therapy, a minority of PWH have detectable HIV RNA in CSF when HIV RNA in blood is undetectable, a condition termed CSF viral escape that can occur with or without symptoms [6, 9–12]. CSF viral escape is associated with ART drugs that do not achieve therapeutic concentrations in the CNS and/or have reduced efficacy as a consequence of drug resistance mutations, among other factors such as worse immune status [6, 8, 13–15]. Newer ART drugs with higher potency, a high genetic barrier to resistance and a longer half-life, such as second-generation integrase strand transfer inhibitors (INSTIs), are more effective at suppressing HIV systemically and typically also do so in the CNS. These attributes have led to efforts to simplify ART regimens to reduce cost, improve medication adherence and limit toxicities. However, concerns exist that simplification approaches could lead to HIV escape in the CNS or other tissues wherein drug distribution and efficacy may be suboptimal [3]. Moreover, if simplified regimens have suboptimal efficacy in the CNS, resurgent HIV replication and resulting immune responses could lead to a greater risk for CNS complications of HIV disease, particularly cognitive and mood disorders [1, 10, 16, 17].The study by Trunfio et al.[18] addresses these concerns by evaluating the efficacy of two-drug ART regimens in the CNS. Trunfio et al.[18] analysed data from a retrospective, cross-sectional study that compared effects of two-drug (n= 19) and three-drug (n= 78) ART regimens on CSF viral suppression, biomarkers of inflammation and neuronal injury, and neurocognitive performance in adults who had lumbar punctures performed between 2010 and 2019. All participants were on the same ART regimen for at least 30 months prior to lumbar puncture and were virally suppressed with plasma HIV RNA below 200 copies/ml for at least 6 months. Two-drug regimens were heterogeneous and included INSTI+ protease inhibitor, INSTI+ NNRTI, PI+ NNRTI and PI+ NRTI regimens. The authors found no statistically significant differences between the two-drug and three-drug regimens with respect to cognitive performance, CSF viral suppression or biomarkers. These results are consistent with prior work indicating that ART regimens that suppress HIV in blood usually suppress HIV in CSF as well.
