Long-Acting Injectable Cabotegravir for HIV Prevention: What Do We Know and Need to Know about the Risks and Consequences of Cabotegravir Resistance?
Long-Acting Injectable Cabotegravir for HIV Prevention: What Do We Know and Need to Know about the Risks and Consequences of Cabotegravir Resistance?
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DOI：
10.1007/s11904-022-00616-y
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发表时间：
2022-10
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
Cabotegravir是一种有效的整合酶链转移抑制剂（CITI），最近被批准为用于预防HIV的长效注射制剂（CAB-LA）。我们总结了体外、猕猴和临床研究中关于cabotegravir药代动力学、活性和耐药性出现的已知信息，并评估了按时注射和CAB-LA停药后CAB-LA耐药性的风险。高水平的cabotegravir耐药性需要多个cabotegravir I突变的积累，相同的突变组合可能导致对dolutegravir的交叉耐药性，dolutegravir广泛用于低收入和中等收入国家的一线抗逆转录病毒治疗。虽然CAB-LA在预防HIV方面非常有效，但在CAB-LA试验中，尽管按时注射，但确实发生了突破性感染，导致选择了单一和组合的CAB-I抗性突变。随着CAB-LA的扩大，及时的艾滋病毒诊断以防止耐药性，耐药性监测可以帮助保持INSTI在艾滋病毒治疗和预防方面的有效性。
Cabotegravir is a potent integrase strand transfer inhibitor (INSTI) recently approved as a long-acting injectable formulation for HIV prevention (CAB-LA). We summarize what is known about cabotegravir pharmacokinetics, activity, and emergence of resistance from in vitro, macaque and clinical studies, and we evaluate the risk of resistance from CAB-LA with on-time injections and after CAB-LA discontinuation. The accumulation of multiple INSTI mutations is required for high-level cabotegravir resistance, and the same mutation combinations may cause cross-resistance to dolutegravir, which is widely used for first-line antiretroviral therapy in low- and middle-income countries. Though CAB-LA was highly effective in preventing HIV, breakthrough infections did occur in trials of CAB-LA despite on-time injections, resulting in selection of single and combinations of INSTI resistance mutations. As CAB-LA is scaled-up, prompt HIV diagnosis to prevent resistance, and resistance monitoring could help preserve the effectiveness of INSTIs for both HIV treatment and prevention.
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影响因子：
15.8
作者：
Baeten JM;Heffron R;Kidoguchi L;Mugo NR;Katabira E;Bukusi EA;Asiimwe S;Haberer JE;Morton J;Ngure K;Bulya N;Odoyo J;Tindimwebwa E;Hendrix C;Marzinke MA;Ware NC;Wyatt MA;Morrison S;Haugen H;Mujugira A;Donnell D;Celum C;Partners Demonstration Project Team
通讯作者：
Partners Demonstration Project Team
DOI：
10.1097/qai.0000000000002409
发表时间：
2020-09-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Blair CS;Li S;Chau G;Cottle L;Richardson P;Marzinke MA;Eshleman SH;Adeyeye A;Rinehart AR;Margolis D;McCauley M;Hendrix CW;Landovitz RJ;HPTN 077 Study Team
通讯作者：
HPTN 077 Study Team
DOI：
10.1126/science.1248707
发表时间：
2014-03-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Andrews CD;Spreen WR;Mohri H;Moss L;Ford S;Gettie A;Russell-Lodrigue K;Bohm RP;Cheng-Mayer C;Hong Z;Markowitz M;Ho DD
通讯作者：
Ho DD
影响因子：
16.1
作者：
Markowitz, Martin;Frank, Ian;Spreen, William R.
通讯作者：
Spreen, William R.
影响因子：
7.3
作者：
Johns, Brian A.;Kawasuji, Takashi;Fujiwara, Tamio
通讯作者：
Fujiwara, Tamio