Hyle Emily P, Bekker Linda-Gail, McCluskey Suzanne M, Chen Wanyi, Sax Paul E, Moosa Mahomed-Yunus, Machoko Munashe, Bangs Audrey, Steegen Kim, Siedner Mark J, van de Vijver David A M C, Resch Stephen C, Neilan Anne M, Phillips Andrew, Walensky Rochelle P, Lessells Richard J, Weinstein Milton C, Dugdale Caitlin M, Wood Robin, Freedberg Kenneth A
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Desmond Tutu HIV Center, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Lancet HIV. 2025 Sep;12(9):e627-e637. doi: 10.1016/S2352-3018(25)00164-X. Epub 2025 Aug 6.
Persistent virological non-suppression among people with HIV receiving tenofovir-lamivudine-dolutegravir (TLD) can result from poor adherence with or without resistance; however, genotypic resistance testing (GRT) is not recommended routinely in South Africa. We examined the clinical and economic effect of GRT for all South African adults diagnosed with persistent virological non-suppression on TLD.
In this modelling study, we used the previously validated Cost-Effectiveness of Preventing AIDS Complications-International microsimulation model to compare three strategies: (1) continued TLD (baseline); (2) immediate switch to tenofovir-lamivudine plus ritonavir-boosted darunavir; and (3) GRT prompting switch to tenofovir-lamivudine plus ritonavir-boosted darunavir for people with dolutegravir resistance or TLD continuation for people without dolutegravir resistance. We estimated that 2·3% and 28·5% of the baseline population have dolutegravir resistance and nucleoside reverse transcriptase inhibitor (NRTI) resistance, respectively. We also examined the effect of a low-cost, point-of-care urine tenofovir test in development to detect recent antiretroviral therapy use (84% sensitivity and 50% specificity), with GRT only when positive. Costs included GRT (US$157 per test), TLD ($45 per year), tenofovir-lamivudine plus ritonavir-boosted darunavir ($247 per year), and urine tenofovir testing ($2 per test). Outcomes included life-years, costs (provider perspective), and incremental cost-effectiveness ratios (ICERs; $ per disability-adjusted life-year [DALY]). We considered cost-effectiveness thresholds of less than $3310 per DALY (base case) and less than $1100 to $4250 per DALY.
Based on our model, we estimated that continued TLD results in 14·11 undiscounted life-years and costs $5380 discounted at 3%; GRT results in 14·36 life-years and costs $5860 (0·14 discounted DALYs averted; ICER $3500 per DALY). Immediate switch results in fewer DALYs averted and higher costs. GRT has an ICER of $3310 per DALY or less when baseline dolutegravir resistance prevalence is ≥2·5% or genotypic resistance test costs ≤$147 per test. Urine tenofovir testing to identify GRT eligibility results in an ICER of $2300 per DALY; the ICER would be less than $1100 per DALY if urine test specificity is 0·87 or greater and costs $2 per test or test specificity is higher than 0·98 and costs $10 per test or less.
GRT could increase life expectancy for people with HIV and persistent virological non-suppression on TLD in South Africa and could be cost-effective, especially at lower test costs. At current effectiveness and costs of tenofovir-lamivudine plus ritonavir-boosted darunavir, an immediate switch would not be preferred.
National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the MGH Jerome and Celia Reich Endowed Scholar in HIV/AIDS Research Award.
接受替诺福韦-拉米夫定-多替拉韦（TLD）治疗的HIV感染者中，持续病毒学未抑制可能是由于依从性差，无论有无耐药；然而，南非不建议常规进行基因型耐药检测（GRT）。我们研究了GRT对所有被诊断为TLD持续病毒学未抑制的南非成年人的临床和经济影响。
在这项建模研究中，我们使用先前验证的预防艾滋病并发症国际微观模拟模型来比较三种策略：（1）继续使用TLD（基线）；（2）立即换用替诺福韦-拉米夫定加利托那韦增强的达芦那韦；（3）对于有多替拉韦耐药的患者，GRT提示换用替诺福韦-拉米夫定加利托那韦增强的达芦那韦，对于无多替拉韦耐药的患者继续使用TLD。我们估计基线人群中分别有2.3%和28.5%的人存在多替拉韦耐药和核苷类逆转录酶抑制剂（NRTI）耐药。我们还研究了一种正在研发的低成本即时检测尿替诺福韦试验的效果，以检测近期抗逆转录病毒治疗的使用情况（灵敏度84%，特异性50%），仅在检测结果为阳性时进行GRT。成本包括GRT（每次检测157美元）、TLD（每年45美元）、替诺福韦-拉米夫定加利托那韦增强的达芦那韦（每年247美元）和尿替诺福韦检测（每次检测2美元）。结果包括生命年数、成本（提供者视角）和增量成本效益比（ICERs；每残疾调整生命年[DALY]的美元数）。我们考虑了每DALY低于3310美元（基础病例）和每DALY低于1100至4250美元的成本效益阈值。
基于我们的模型，我们估计继续使用TLD可带来14.11个未贴现生命年，按3%贴现后的成本为5380美元；GRT可带来14.36个生命年，成本为5860美元（避免0.14个贴现DALY；ICER为每DALY 3500美元）。立即换药避免的DALY较少且成本较高。当基线多替拉韦耐药患病率≥2.5%或基因型耐药检测成本≤每次检测147美元时，GRT的ICER为每DALY 3310美元或更低。使用尿替诺福韦检测来确定是否适合进行GRT，ICER为每DALY 2300美元；如果尿检测特异性为0.87或更高且每次检测成本为2美元，或检测特异性高于0.98且每次检测成本为10美元或更低，则ICER将低于每DALY 1100美元。
GRT可以提高南非接受TLD治疗且持续病毒学未抑制的HIV感染者的预期寿命，并且可能具有成本效益，尤其是在检测成本较低的情况下。按照目前替诺福韦-拉米夫定加利托那韦增强的达芦那韦的有效性和成本，立即换药并非首选。
美国国立过敏与传染病研究所、尤妮斯·肯尼迪·施赖弗国立儿童健康与人类发展研究所，以及MGH杰罗姆和西莉亚·赖希HIV/AIDS研究捐赠奖学金。
