Health Economics and Decision Science (HEDS), School for Health and Related Research, University of Sheffield, Sheffield, United Kingdom.
Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa.
J Acquir Immune Defic Syndr. 2020 May 1;84(1):107-113. doi: 10.1097/QAI.0000000000002313.
After failure of first-line antiretroviral therapy (ART) in the public sector, delayed or missed second-line ART switch is linked with poor outcomes in patients with advanced HIV.
We investigated delayed or missed second-line ART switch after confirmed virologic failure in the largest private sector HIV cohort in Africa.
We included HIV-infected adults with confirmed virologic failure after 6 months of nonnucleoside reverse-transcriptase inhibitor-based ART. We estimated the effect of timing of switch on the hazard of death using inverse probability of treatment weighting of marginal structural models. We adjusted for time-dependent confounding of CD4 count, viral load, and visit frequency.
Five thousand seven hundred forty-eight patients (53% female) with confirmed virologic failure met inclusion criteria; the median age was 40 [interquartile range (IQR): 35-47], advanced HIV was present in 48% and the prior duration of nonnucleoside reverse-transcriptase inhibitor-based ART was 1083 days (IQR: 665-1770). Median time to confirmation of virologic failure and to second-line switch was 196 (IQR: 136-316) and 220 days (IQR: 65-542), respectively. Switching to second-line ART after confirmed failure compared with remaining on first-line ART reduced risk of subsequent death [adjusted hazard ratio: 0.47 (95% confidence interval: 0.36 to 0.63)]. Compared with patients who experienced delayed switch, those switched immediately had a lower risk of death, regardless of CD4 cell count.
Delayed or missed switch to second-line ART after confirmed first-line ART failure is common in the South African private sector and associated with mortality. Novel interventions to minimize switch delay should be tested and not limited to those with advanced disease at treatment failure.
在公共部门一线抗逆转录病毒疗法（ART）治疗失败后，二线 ART 延迟或错过转换与晚期 HIV 患者的不良结局相关。
我们调查了在非洲最大的私人部门 HIV 队列中确认病毒学失败后二线 ART 转换的延迟或错过。
我们纳入了在基于非核苷逆转录酶抑制剂的 ART 治疗 6 个月后确认病毒学失败的 HIV 感染成年人。我们使用边缘结构模型的逆概率治疗加权来估计转换时间对死亡风险的影响。我们调整了 CD4 计数、病毒载量和就诊频率的时变混杂。
5748 例（53%为女性）确认病毒学失败的患者符合纳入标准；中位年龄为 40 岁（四分位距[IQR]：35-47），48%的患者 HIV 处于晚期，基于非核苷逆转录酶抑制剂的 ART 先前持续时间为 1083 天（IQR：665-1770）。确认病毒学失败和二线转换的中位时间分别为 196 天（IQR：136-316）和 220 天（IQR：65-542）。与继续一线 ART 相比，在确认失败后转换至二线 ART 降低了随后死亡的风险[调整后的危险比：0.47（95%置信区间：0.36 至 0.63）]。与延迟转换的患者相比，无论 CD4 细胞计数如何，立即转换的患者死亡风险较低。
在南非私人部门，确认一线 ART 治疗失败后二线 ART 转换的延迟或错过很常见，并且与死亡率相关。应测试新的干预措施以尽量减少转换延迟，而不仅仅局限于治疗失败时疾病已处于晚期的患者。
