Service de Médecine Interne, APHP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
INSERM, U1016, CNRS, UMR8104, Institut Cochin, Paris, France.
J Antimicrob Chemother. 2022 Aug 25;77(9):2506-2515. doi: 10.1093/jac/dkac207.
Whether integrase strand transfer inhibitors (INSTIs) can decrease HIV-1 DNA levels more rapidly than boosted PIs during primary HIV-1 infection (PHI) is unknown. We hypothesized that once-daily dolutegravir/tenofovir/emtricitabine could reduce the viral reservoir through rapid viral replication control further than once-daily darunavir/cobicistat/tenofovir/emtricitabine.
The OPTIPRIM2-ANRS 169 study was a randomized (1:1), open-label, multicentre trial in adults with ≤5 or ≤3 HIV antibodies detected, respectively, by western blot or immunoblot in the last 10 days. The primary endpoint was total HIV-1 DNA levels in PBMCs at Week 48 (W48) adjusted for baseline levels. The main secondary endpoint was HIV-1 RNA level decrease.
Between April 2017 and August 2018, 101 patients were included from 31 hospitals. Most patients were men (93%), the median age was 36 years and 17% were Fiebig stage ≤3. The median (IQR) plasma HIV-1 RNA and DNA levels were, respectively, 5.8 (5.0-6.6) and 3.87 (3.52-4.15) log10 copies/million PBMCs. The median (IQR) decreases in HIV-1 DNA levels at W48 were -1.48 (-1.74 to -1.06) and -1.39 (-1.55 to -0.98) log10 copies/million PBMCs in the dolutegravir and darunavir/cobicistat groups, respectively (P = 0.52). Plasma HIV-1 RNA levels were <50 copies/mL in 24% versus 0% of patients in the dolutegravir and darunavir/cobicistat groups at W4, 55% versus 2% at W8, 67% versus 17% at W12, and 94% versus 90% at W48, respectively.
Dolutegravir-based and darunavir-based regimens initiated during PHI strongly and similarly decreased the blood reservoir size. Considering the rapid viral suppression during a period of high HIV-1 transmission risk, dolutegravir-based regimens are a major first-line option.
在原发性 HIV-1 感染（PHI）期间，整合酶链转移抑制剂（INSTIs）是否比强化蛋白酶抑制剂（PI）更快地降低 HIV-1 DNA 水平尚不清楚。我们假设，每日一次的多替拉韦/替诺福韦/恩曲他滨可能通过快速控制病毒复制，比每日一次的达芦那韦/考比司他/替诺福韦/恩曲他滨更能降低病毒储存库。
OPTIPRIM2-ANRS 169 研究是一项在成人中进行的随机（1:1）、开放标签、多中心试验，分别在最后 10 天内通过 Western blot 或免疫印迹检测到≤5 或≤3 个 HIV 抗体。主要终点是调整基线水平后的第 48 周（W48）时 PBMC 中的总 HIV-1 DNA 水平。主要次要终点是 HIV-1 RNA 水平下降。
2017 年 4 月至 2018 年 8 月，从 31 家医院纳入了 101 名患者。大多数患者为男性（93%），中位年龄为 36 岁，17%的患者 Fiebig 分期≤3。中位（IQR）血浆 HIV-1 RNA 和 DNA 水平分别为 5.8（5.0-6.6）和 3.87（3.52-4.15）log10 拷贝/百万 PBMCs。W48 时 HIV-1 DNA 水平的中位（IQR）下降分别为多替拉韦组-1.48（-1.74 至-1.06）和达芦那韦/考比司他组-1.39（-1.55 至-0.98）log10 拷贝/百万 PBMCs（P=0.52）。在第 4、8、12 和 48 周时，多替拉韦组分别有 24%和 0%的患者血浆 HIV-1 RNA 水平<50 拷贝/mL，达芦那韦/考比司他组分别有 55%和 2%、55%和 2%、67%和 17%、94%和 90%。
在 PHI 期间启动的基于多替拉韦和基于达芦那韦的方案均强烈且相似地降低了血液储存库大小。考虑到在高 HIV-1 传播风险期间快速病毒抑制，基于多替拉韦的方案是主要的一线选择。
