Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Curr Opin HIV AIDS. 2022 Jul 1;17(4):213-221. doi: 10.1097/COH.0000000000000746.
To review current laboratory and clinical data on the frequency and relative risk of drug resistance and range of mutations selected from approved and investigational antiretroviral agents used for preexposure prophylaxis (PrEP) of HIV-1 infection, including tenofovir disproxil fumarate (TDF)-based oral PrEP, dapivirine ring, injectable cabotegravir (CAB), islatravir, lenacapavir and broadly neutralizing antibodies (bNAbs).
The greatest risk of HIV-1 resistance from PrEP with oral TDF/emtricitabine (FTC) or injectable CAB is from starting or continuing PrEP after undiagnosed acute HIV infection. By contrast, the dapivirine intravaginal ring does not appear to select nonnucleoside reverse transcriptase inhibitor resistance in clinical trial settings. Investigational inhibitors including islatravir, lenacapavir, and bNAbs are promising for use as PrEP due to their potential for sustained delivery and low risk of cross-resistance to currently used antiretrovirals, but surveillance for emergence of resistance mutations in more HIV-1 gene regions (gag, env) will be important as the same drugs are being developed for HIV therapy.
PrEP is highly effective in preventing HIV infection. Although HIV drug resistance from PrEP use could impact future options in individuals who seroconvert on PrEP, the current risk is low and continued monitoring for the emergence of resistance and cross-resistance during product development, clinical studies, and product roll-out is advised to preserve antiretroviral efficacy for both treatment and prevention.
回顾目前关于批准和研究中的抗逆转录病毒药物用于预防 HIV-1 感染的药物耐药性和突变选择频率及范围的实验室和临床数据，这些药物包括富马酸替诺福韦二吡呋酯（TDF）为基础的口服暴露前预防（PrEP）、双夫定阴道环、注射用卡博特韦（CAB）、伊拉司韦、lenacapavir 和广谱中和抗体（bNAbs）。
使用 TDF/恩曲他滨（FTC）或注射用 CAB 进行 PrEP 时，最大的 HIV-1 耐药风险来自于在未确诊的急性 HIV 感染后开始或继续 PrEP。相比之下，双夫定阴道环在临床试验环境中似乎不会选择非核苷类逆转录酶抑制剂耐药。伊拉司韦、lenacapavir 和 bNAbs 等研究抑制剂由于其持续递送的潜力和与目前使用的抗逆转录病毒药物交叉耐药的风险低，有望用于 PrEP，但需要对更多 HIV-1 基因区域（ gag 、 env ）的耐药突变出现进行监测，因为相同的药物正在开发用于 HIV 治疗。
PrEP 非常有效地预防 HIV 感染。尽管 PrEP 用药引起的 HIV 耐药性可能会影响在 PrEP 上发生血清转换的个体未来的治疗选择，但目前的风险较低，在产品开发、临床研究和产品推出过程中，建议继续监测耐药性和交叉耐药性的出现，以保持抗逆转录病毒疗效，无论是用于治疗还是预防。
