Cardoso Sandra W, Grinsztejn Beatriz, Velasque Luciane, Veloso Valdilea G, Luz Paula M, Friedman Ruth K, Morgado Mariza, Ribeiro Sayonara R, Moreira Ronaldo I, Keruly Jeanne, Moore Richard D
Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
AIDS Res Hum Retroviruses. 2010 Aug;26(8):865-74. doi: 10.1089/aid.2009.0274.
Studies on the long-term safety and tolerability of HAART are scarce in developing countries. HAART has been universally available in Brazil since 1997, providing a unique opportunity to evaluate the incidence and risk factors for HAART discontinuation or modification. We analyzed retrospective data from 670 treatment-naive patients followed at the HIV cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, in Rio de Janeiro, Brazil, who first received HAART between January 1996 and December 2006. Our four outcomes of interest were treatment failure (TF-MOD), short-term toxicity (ST-MOD), long-term toxicity (LT-MOD), and overall modification/discontinuation (MOD, composed of TF-MOD, ST-MOD, LT-MOD, and other reasons). Risk factors were assessed using Cox's proportional hazards regression. Incidences of MOD, ST-MOD, LT-MOD, and TF-MOD were 28.3, 24.0, 4.0, and 5.6 per 100 persons-years, respectively. MOD was observed in 69% of the patients; 40% of the MODs were toxicity related. The risk of MOD in the first year of treatment was 32% (95% CI: 28.3-35.5%); the median time from HAART initiation to MOD was 14 months (IQR: 3.0-29.5). The most frequent reasons for ST-MOD were gastrointestinal; women had a higher hazard for ST-MOD. Metabolic toxicity was the most frequent reason for LT- MOD, particularly dislipidemia and lipodystrophy. Increased hazard of TF-MOD was observed among those with lower CD4(+) lymphocyte counts (<200 cells/mm(3)). Our results indicate that toxicities can compromise adherence and thus impact future treatment options. This is especially relevant in the context of limited access to second and third line treatment regimens.
在发展中国家，关于高效抗逆转录病毒治疗（HAART）长期安全性和耐受性的研究很少。自1997年以来，HAART在巴西已普遍可用，这为评估HAART停药或调整的发生率及风险因素提供了独特机会。我们分析了巴西里约热内卢奥斯瓦尔多·克鲁兹基金会埃万德罗·查加斯临床研究所HIV队列中670例初治患者的回顾性数据，这些患者于1996年1月至2006年12月首次接受HAART治疗。我们感兴趣的四个结局是治疗失败（TF-MOD）、短期毒性（ST-MOD）、长期毒性（LT-MOD）以及总体调整/停药（MOD，由TF-MOD、ST-MOD、LT-MOD和其他原因组成）。使用Cox比例风险回归评估风险因素。MOD、ST-MOD、LT-MOD和TF-MOD的发生率分别为每100人年28.3、24.0、4.0和5.6例。69%的患者出现了MOD；其中40%的MOD与毒性有关。治疗第一年出现MOD的风险为32%（95%CI：28.3 - 35.5%）；从开始HAART到出现MOD的中位时间为14个月（IQR：3.0 - 29.5）。ST-MOD最常见的原因是胃肠道问题；女性出现ST-MOD的风险更高。代谢毒性是LT-MOD最常见的原因，尤其是血脂异常和脂肪代谢障碍。CD4(+)淋巴细胞计数较低（<200个细胞/mm³）的患者中观察到TF-MOD的风险增加。我们的结果表明，毒性可能会影响依从性，从而影响未来的治疗选择。在二线和三线治疗方案获取有限的情况下，这一点尤为重要。
