Sibale Lusako L, Kalata Newton, Mitole Ndaona, Nyazika Tinashe K, Phiri Joseph A, Kusakala Alice, Khwiya Mercy, Sagawa Gift, Lo Stephanie W, Chaguza Chrispin, Thindwa Deus, Swarthout Todd D, French Neil, Malisita Ken, Kamng'ona Arox, Ferreira Daniela M, Bentley Stephen D, Heyderman Robert S, Kwambana-Adams Brenda A, Jambo Kondwani C
Infection and Immunity Research Group, Malawi-Liverpool-Wellcome Programme, Blantyre, Malawi.
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
Open Forum Infect Dis. 2025 Jul 16;12(8):ofaf422. doi: 10.1093/ofid/ofaf422. eCollection 2025 Aug.
People living with human immunodeficiency virus (HIV; PLHIV) on antiretroviral therapy (ART) are still at risk of pneumococcal disease and have over 2-fold higher pneumococcal carriage prevalence than HIV-uninfected (HIV-) adults). Carriage is a risk factor for pneumococcal disease, antimicrobial resistance (AMR) emergence, and transmission. Therefore, we tested whether the high prevalence of pneumococcal carriage in PLHIV on ART is associated with increased bacterial density, shedding, and AMR.
We recruited asymptomatic PLHIV on ART for >1 year (PLHIV-ART>1y) and HIV- adults. Nasopharyngeal swab samples were collected on days 3, 7, 14, 21, and 28, followed by monthly collections for 12 months, while shedding samples were collected on days 3, 21, and 28. Peripheral blood samples were collected on day 3 to measure CD4 cell count and HIV viral load. Pneumococcal carriage density and shedding were assessed using standard bacterial culture, multiple carriage was detected using whole-plate sweep sequencing, and AMR profiling was conducted using disk diffusion and Etest.
PLHIV-ART>1y had a higher propensity for high-density carriage (adjusted odds ratio, 1.67 [95% confidence interval (CI), 1.07-2.60]; = .02). Moreover, PLHIV-ART>1y are more likely to shed pneumococci than HIV- adults (adjusted odds ratio, 2.52 [95% CI, 1.06-6.00]; = .04), with carriage density identified as an important risk factor for shedding (3.35 [1.55-7.24]; = .002). Aerosol shed isolates from PLHIV-ART>1y were mostly multidrug resistant (18 of 29 [ 62%; 95% CI, 48%-77%]).
These findings indicate that PLHIV-ART>1y remain at high risk of pneumococcal disease and could also be an important reservoir for shedding multidrug-resistant pneumococci.
接受抗逆转录病毒治疗（ART）的人类免疫缺陷病毒（HIV）感染者（PLHIV）仍有患肺炎球菌疾病的风险，其肺炎球菌携带率比未感染HIV的成年人高出两倍多。携带是肺炎球菌疾病、抗菌药物耐药性（AMR）出现和传播的危险因素。因此，我们测试了接受ART的PLHIV中肺炎球菌携带率高是否与细菌密度增加、脱落及AMR有关。
我们招募了接受ART超过1年的无症状PLHIV（PLHIV-ART>1y）和未感染HIV的成年人。在第3、7、14、21和28天采集鼻咽拭子样本，随后在12个月内每月采集一次，同时在第3、21和28天采集脱落样本。在第3天采集外周血样本以测量CD4细胞计数和HIV病毒载量。使用标准细菌培养评估肺炎球菌携带密度和脱落情况，使用全板扫描测序检测多重携带情况，并使用纸片扩散法和Etest进行AMR分析。
PLHIV-ART>1y有更高的高密度携带倾向（调整优势比，1.67[95%置信区间（CI），1.07 - 2.60]；P = 0.02）。此外，PLHIV-ART>1y比未感染HIV的成年人更有可能排出肺炎球菌（调整优势比，2.52[95%CI，1.06 - 6.00]；P = 0.04），携带密度被确定为脱落的重要危险因素（3.35[1.55 - 7.24]；P = 0.002）。从PLHIV-ART>1y排出的气溶胶分离株大多具有多重耐药性（29株中有18株[62%；95%CI，48% - 77%]）。
这些发现表明，PLHIV-ART>1y仍然面临肺炎球菌疾病的高风险，也可能是多重耐药肺炎球菌脱落的重要储存库。
