Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg Sahlgrenska Academy, Gothenburg, Sweden
Department of Infectious Diseases, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
BMJ Open. 2023 May 17;13(5):e070693. doi: 10.1136/bmjopen-2022-070693.
In order to enable long-term follow-up of the natural course of HIV infection in the central nervous system, a longitudinal cohort study with repeated cerebrospinal fluid (CSF) analyses at intervals over time was initiated in 1985. When antiretrovirals against HIV were introduced in the late 1980s, short-term and long-term effects of various antiretroviral treatment (ART) regimens were added to the study.
All adult people living with HIV (PLWH) who were diagnosed at or referred to the Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, Sweden were asked to participate in the Gothenburg HIV CSF Study Cohort. PLWH with neurological symptoms or other clinical symptoms of HIV, as well as those with no symptoms of HIV infection, were included. Most participants were asymptomatic, which distinguishes this cohort from most other international HIV CSF studies. In addition, HIV-negative controls were recruited. These included people on HIV pre-exposure prophylaxis who served as lifestyle-matched controls to HIV-infected men who have sex with men. Since lumbar puncture (LP) is an invasive procedure, some PLHW only consented to participate in one examination. Furthermore, at the beginning of the study, several participants were lost to follow-up having died from AIDS. Of 662 PLWH where an initial LP was done, 415 agreed to continue with follow-up. Among the 415, 56 only gave permission to be followed with LP for less than 1 year, mainly to analyse the short-term effect of ART. The remaining 359 PLWH were followed up with repeated LP for periods ranging from >1 to 30 years. This group was defined as the 'longitudinal cohort'. So far, on 7 April 2022, 2650 LP and samplings of paired CSF/blood had been performed, providing a unique biobank.
A general finding during the 37-year study period was that HIV infection in the central nervous system, as mirrored by CSF findings, appears early in the infectious course of the disease and progresses slowly in the vast majority of untreated PLWH. Combination ART has been highly effective in reducing CSF viral counts, inflammation and markers of neural damage. Minor CSF signs of long-term sequels or residual inflammatory activity and CSF escape (viral CSF blips) have been observed during follow-up. The future course of these changes and their clinical impact require further studies.
PLWH today have a life expectancy close to that of non-infected people. Therefore, our cohort provides a unique opportunity to study the long-term effects of HIV infection in the central nervous system and the impact of ART and is an ongoing study.
为了能够对 HIV 感染在中枢神经系统中的自然病程进行长期随访，我们于 1985 年启动了一项纵向队列研究，该研究对脑脊液（CSF）进行了多次分析，时间跨度较长。在 20 世纪 80 年代末引入抗 HIV 药物后，我们将各种抗逆转录病毒治疗（ART）方案的短期和长期效果添加到研究中。
所有在瑞典哥德堡萨尔格勒纳大学医院传染病科诊断或转介的成年 HIV 感染者（PLWH）均被邀请参加哥德堡 HIV CSF 研究队列。具有神经症状或其他 HIV 临床症状的 PLWH，以及无症状的 HIV 感染者，均被纳入研究。大多数参与者无症状，这与大多数其他国际 HIV CSF 研究不同。此外，还招募了 HIV 阴性对照者。这些人包括正在接受 HIV 暴露前预防的人群，他们作为性取向为男男性行为的 HIV 感染者的生活方式匹配对照者。由于腰椎穿刺（LP）是一种有创性操作，因此一些 PLHW 仅同意参加一次检查。此外，在研究开始时，一些参与者因 AIDS 而死亡，从而导致失访。在进行首次 LP 的 662 名 PLWH 中，有 415 人同意继续进行随访。在这 415 人中，仅有 56 人仅允许 LP 随访时间不足 1 年，主要是为了分析 ART 的短期效果。其余 359 名 PLWH 则进行了 LP 随访，时间从 1 年以上到 30 年不等。该组被定义为“纵向队列”。截至 2022 年 4 月 7 日，已经进行了 2650 次 LP 和 CSF/血液配对采样，提供了一个独特的生物库。
在 37 年的研究期间，一个普遍的发现是，HIV 在中枢神经系统中的感染，如 CSF 结果所反映的，在疾病的感染过程早期出现，并在绝大多数未经治疗的 PLWH 中缓慢进展。联合 ART 已被证明可有效降低 CSF 病毒载量、炎症和神经损伤标志物。在随访过程中观察到了轻微的 CSF 长期后遗症或残留炎症活动和 CSF 逃逸（病毒 CSF 闪烁）迹象。这些变化的未来进程及其临床影响需要进一步研究。
如今，PLWH 的预期寿命接近未感染者。因此，我们的队列为研究 HIV 感染在中枢神经系统中的长期影响以及 ART 的影响提供了一个独特的机会，并且是一个正在进行的研究。
