Marzinke Mark A, Grinsztejn Beatriz, Fogel Jessica M, Piwowar-Manning Estelle, Li Maoji, Weng Lei, McCauley Marybeth, Cummings Vanessa, Ahmed Shahnaz, Haines Casey D, Bushman Lane R, Petropoulos Christos, Persaud Deborah, Adeyeye Adeola, Kofron Ryan, Rinehart Alex, St Clair Marty, Rooney James F, Pryluka Daniel, Coelho Lara, Gaur Aditya, Middelkoop Keren, Phanuphak Nittaya, Cohen Myron S, Hendrix Craig W, Anderson Peter, Hanscom Brett, Donnell Deborah, Landovitz Raphael J, Eshleman Susan H
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Infect Dis. 2021 Nov 16;224(9):1581-1592. doi: 10.1093/infdis/jiab152.
The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083.
Retrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing.
Fifty-eight infections were evaluated, including 51 incident infections (12 in CAB arm and 39 in TDF/FTC arm). In many cases (5 in CAB arm and 37 in TDF/FTC arm), infection was associated with low or unquantifiable study drug concentrations. In 4 cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral therapy, and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing.
Early detection of HIV infection and prompt antiretroviral therapy initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.
艾滋病预防试验网络（HPTN）083试验表明，在预防男同性恋和顺性别男性中感染人类免疫缺陷病毒（HIV）方面，长效卡博特韦（CAB-LA）比替诺福韦酯-恩曲他滨（TDF/FTC）更有效。我们对HPTN 083盲法阶段发生的HIV感染进行了特征描述。
回顾性检测包括HIV检测、病毒载量检测、研究药物定量以及HIV耐药性检测。
评估了58例感染，包括51例新发感染（CAB组12例，TDF/FTC组39例）。在许多情况下（CAB组5例，TDF/FTC组37例），感染与研究药物浓度低或无法定量有关。在4例中，感染发生在按时注射CAB-LA且血浆CAB浓度预期的情况下。CAB暴露与病毒抑制延长和抗体表达延迟有关。在某些情况下，HIV诊断延迟导致向未检测到感染的参与者提供CAB、抗逆转录病毒治疗延迟以及耐药性出现；如果进行病毒载量检测，这些感染中的大多数本可以更早被检测到。
尽管进行了CAB-LA预防，但早期检测HIV感染并及时启动抗逆转录病毒治疗可改善感染者的临床结局。需要进一步研究以阐明接受CAB-LA者HIV保护的相关因素。
