Amsterdam Institute for Global Health and Development, and Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
African Society of Laboratory Medicine, Addis Ababa, Ethiopia.
AIDS. 2018 May 15;32(8):1043-1051. doi: 10.1097/QAD.0000000000001801.
To assess incidence, determinants and clinical consequences of suboptimal immune recovery in HIV-1 infected adults in sub-Saharan Africa with sustained viral suppression on antiretroviral therapy (ART).
Multicountry prospective cohort.
Suboptimal immune recovery was defined as proportions of participants who failed to attain clinically relevant CD4+ cell count thresholds (>200, >350 and >500 cells/μl) despite sustained viral suppression on continuous first-line ART. Participants were censored at the earliest of death, loss to follow-up, last viral load less than 50 copies/ml, or database closure. Determinants of immune recovery were assessed using multivariable Cox regression. We estimated incidence rates of AIDS, pulmonary tuberculosis and all-cause mortality for CD4+ strata.
One thousand, five hundred and ninety-two participants were included; 60% were women, median age was 37 years (IQR 31-43) and median pre-ART CD4+ cell count was 147 cells/μl (IQR 76-215). After 6 years of ART, suboptimal immune recovery at CD4+ cell counts less than 200 cells/μl, less than 350 cells/μl, and less than 500 cells/μl occurred in 7, 27, and 57% of participants, respectively. Compared with participants with CD4+ cell count greater than 500 cells/μl, on-ART incidence rates were 12.5, 4.1, 0.9 times higher for AIDS and 16.9, 3.5, and 2.3 times higher for pulmonary tuberculosis in participants with CD4+ cell count less than 200, 200-349, and 350-499 cells/μl, respectively. All-cause mortality was highest in participants with CD4+ cell count less than 200 cells/μl, and comparable across the higher CD4+ strata. Older age, male sex, and lower pre-ART CD4+ cell count were strongly associated with suboptimal immune recovery.
These findings warrant close clinical and laboratory monitoring until adequate immune reconstitution is achieved and support early ART initiation before decline of CD4+ cell count.
评估撒哈拉以南非洲地区 HIV-1 感染成年人在接受抗逆转录病毒治疗（ART）后病毒持续抑制但免疫恢复不理想的发生率、决定因素和临床后果。
多国家前瞻性队列研究。
免疫恢复不理想定义为尽管接受连续一线 ART 治疗病毒持续抑制，但未能达到临床相关 CD4+细胞计数阈值（>200、>350 和>500 个/μl）的参与者比例。参与者在以下最早的情况下被删失：死亡、失访、最后一次病毒载量<50 拷贝/ml 或数据库关闭。使用多变量 Cox 回归评估免疫恢复的决定因素。我们根据 CD4+细胞计数分层估计 AIDS、肺结核和全因死亡率的发生率。
共纳入 1592 名参与者；60%为女性，中位年龄为 37 岁（IQR 31-43），中位 ART 前 CD4+细胞计数为 147 个/μl（IQR 76-215）。在接受 ART 治疗 6 年后，CD4+细胞计数<200 个/μl、<350 个/μl 和<500 个/μl 的参与者中分别有 7%、27%和 57%出现免疫恢复不理想。与 CD4+细胞计数>500 个/μl 的参与者相比，CD4+细胞计数<200、200-349 和 350-499 个/μl 的参与者发生 AIDS 的 ART 发生率分别为 12.5、4.1 和 0.9 倍，发生肺结核的 ART 发生率分别为 16.9、3.5 和 2.3 倍。CD4+细胞计数<200 个/μl 的参与者全因死亡率最高，而在较高的 CD4+细胞计数分层中死亡率相当。年龄较大、男性和较低的 ART 前 CD4+细胞计数与免疫恢复不理想密切相关。
这些发现表明需要密切的临床和实验室监测，直到获得足够的免疫重建，并支持在 CD4+细胞计数下降之前尽早开始 ART。
