Meintjes Graeme, Dunn Liezl, Coetsee Marla, Hislop Michael, Leisegang Rory, Regensberg Leon, Maartens Gary
Clinical Infectious Diseases Research Initiative (CIDRI), Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925 South Africa ; Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa ; Department of Medicine, Imperial College London, London, UK.
Aid for AIDS Management, Afrocentric Health Pty Ltd, The Boulevard, Block G, Searle Street, Woodstock, 7925 South Africa.
AIDS Res Ther. 2015 Dec 1;12:39. doi: 10.1186/s12981-015-0081-8. eCollection 2015.
An increasing number of patients in Africa are experiencing virologic failure on second-line antiretroviral therapy (ART) and those who develop resistance to protease inhibitors (PI) will require third-line ART, but no data on the outcomes of third-line are available from the region. We assessed the virologic outcomes and survival of patients started on salvage ART in a Southern African private sector disease management programme.
Retrospective observational cohort study with linkage to the national death register. Adults (≥18 years) who started salvage ART between July 2007 and December 2011 were included. Salvage ART was defined by inclusion of darunavir or tipranavir in an ART regimen after having failed another PI. For Kaplan-Meier (KM) analysis, patients were followed up until event, or censored at death (only for virologic outcomes), leaving the programme, or April 2014.
152 patients were included. Subtype was known for 113 patients: 111 (98 %) were infected with subtype C. All 152 had a genotype resistance test demonstrating major PI resistance mutations. Salvage drugs included were: darunavir/ritonavir (n = 149), tipranavir/ritonavir (n = 3), raltegravir (n = 58), and etravirine (n = 8). Median follow-up was 2.5 years (IQR = 1.5-3.3). 82.9 % achieved a viral load ≤400 copies/ml and 71.1 % ≤50 copies/ml. By the end of the study 17 (11.2 %) of the patients had died. The KM estimate of cumulative survival was 87.2 % at 2000 days.
Virologic suppression was comparable to that demonstrated in clinical trials and observational studies of salvage ART drugs conducted in other regions. Few deaths occurred during short term follow-up. Third-line regimens for patients with multidrug resistant subtype C HIV in Africa are virologically and clinically effective.
非洲越来越多的患者在二线抗逆转录病毒疗法（ART）上出现病毒学失败，而那些对蛋白酶抑制剂（PI）产生耐药性的患者将需要三线ART，但该地区尚无关于三线治疗结果的数据。我们评估了在南部非洲私营部门疾病管理项目中开始接受挽救性ART治疗的患者的病毒学结果和生存率。
一项与国家死亡登记处相关联的回顾性观察队列研究。纳入2007年7月至2011年12月期间开始接受挽救性ART治疗的成年人（≥18岁）。挽救性ART的定义是在另一种PI治疗失败后，在ART方案中加入达芦那韦或替拉那韦。对于Kaplan-Meier（KM）分析，对患者进行随访直至发生事件，或在死亡时（仅用于病毒学结果）、退出该项目或2014年4月进行截尾。
纳入152例患者。113例患者的亚型已知：111例（98%）感染C亚型。所有152例患者均进行了基因型耐药性检测，显示存在主要的PI耐药突变。所使用的挽救药物包括：达芦那韦/利托那韦（n = 149）、替拉那韦/利托那韦（n = 3）、拉替拉韦（n = 58）和依曲韦林（n = 8）。中位随访时间为2.5年（四分位间距 = 1.5 - 3.3）。82.9%的患者病毒载量≤400拷贝/ml，71.1%的患者≤50拷贝/ml。到研究结束时，17例（11.2%）患者死亡。在2000天时，KM估计的累积生存率为87.2%。
病毒学抑制与在其他地区进行的挽救性ART药物临床试验和观察性研究中所显示的情况相当。在短期随访期间很少发生死亡。非洲多药耐药C亚型HIV患者的三线治疗方案在病毒学和临床上是有效的。
