Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Avenue, P.O. Box 241, Cape Town, 8000, South Africa.
Department of Medical Microbiology, College of Health Sciences, University of Zimbabwe, P.O. Box A178, Avondale, Harare, 00263, Zimbabwe.
J Neurovirol. 2020 Dec;26(6):920-928. doi: 10.1007/s13365-020-00882-9. Epub 2020 Jul 31.
It is not known if proviral DNA in the periphery corresponds to cognitive status in clade C as it does in clade B and recombinant forms. A cross-sectional study was conducted on participants investigated for HIV-associated neurocognitive impairment in South Africa. HIV-1 proviral DNA was quantified using a PCR assay targeting a highly conserved HIV-1 LTR-gag region. Fifty-four (36.7%) participants were cognitively impaired and 93 (63.3%) were not impaired. Forty-three (79.6%) of the cognitively impaired participants were female and 11 (20.4%) were male. There was no significant age difference between cognitively impaired and unimpaired participants (p = 0.42). HIV-1 DNA in cognitively impaired PLWH was significantly higher than in cognitively normal individuals (p = .016). Considering impaired participants, lymphocyte HIV-1 DNA was significantly higher in males than females (p = 0.02). There was a modest positive correlation between lymphocyte HIV-1 DNA and global deficit scores (GDS) r = 0.176; p = 0.03). The two measures of viral load, lymphocyte HIV-1 DNA copies/million and plasma RNA copies/ml, were positively correlated (r = 0.39; p < .001). After adjusting for other covariates, age, sex, treatment status, and the interactions between impairment and treatment, the multivariate regression showed association between proviral load and neurocognitive impairment; omega effect size was 0.04, p value = 0.010. The burden of HIV-1 peripheral blood lymphocyte proviral DNA corresponds to neurocognitive impairment among individuals infected with clade C disease. Therefore, therapeutic strategies to reduce the HIV-1 proviral DNA reservoir in lymphocytes may improve neurocognitive outcomes in PLWH.
目前尚不清楚外周组织中的前病毒 DNA 是否与 C 型 clade 中的认知状态相对应，就像 B 型 clade 和重组形式一样。本研究在南非对 HIV 相关神经认知障碍的参与者进行了横断面研究。使用针对高度保守的 HIV-1 LTR-gag 区域的 PCR 检测方法定量 HIV-1 前病毒 DNA。54 名（36.7%）参与者存在认知障碍，93 名（63.3%）无认知障碍。在认知障碍参与者中，43 名（79.6%）为女性，11 名（20.4%）为男性。认知障碍和无认知障碍参与者之间的年龄无显著差异（p=0.42）。认知障碍 PLWH 中的 HIV-1 DNA 显著高于认知正常个体（p=0.016）。考虑到认知障碍参与者，男性的淋巴细胞 HIV-1 DNA 显著高于女性（p=0.02）。淋巴细胞 HIV-1 DNA 与全球缺陷评分（GDS）之间存在适度的正相关关系（r=0.176;p=0.03）。两种病毒载量测量方法，即淋巴细胞 HIV-1 DNA 拷贝/百万和血浆 RNA 拷贝/ml，呈正相关（r=0.39;p<0.001）。在校正其他协变量、年龄、性别、治疗状况以及障碍和治疗之间的相互作用后，多元回归显示前病毒载量与神经认知障碍之间存在关联；omega 效应大小为 0.04，p 值=0.010。C 型 clade 感染个体外周血淋巴细胞前病毒 DNA 的负担与神经认知障碍相对应。因此，减少 HIV-1 前病毒 DNA 储库的治疗策略可能会改善 PLWH 的神经认知结局。
