Kanthula Ruth, Rossouw Theresa M, Feucht Ute D, van Dyk Gisela, Beck Ingrid A, Silverman Rachel, Olson Scott, Salyer Christen, Cassol Sharon, Frenkel Lisa M
aUniversity of Washington bSeattle Children's Research Institute, Seattle, Washington, USA cUniversity of Pretoria, Pretoria, South Africa.
AIDS. 2017 May 15;31(8):1143-1148. doi: 10.1097/QAD.0000000000001446.
We set out to examine the prevalence and persistence of mutations conferring high-level nonnucleoside reverse transcriptase (NNRTI)-resistance in a cohort of HIV-infected children who had failed prophylaxis to prevent mother-to-child-transmission (PMTCT).
A prospective observational cohort study at the Pediatric HIV Clinic at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa.
Children referred for initiation of antiretroviral therapy (ART) were enrolled from July 2010 through February 2013. HIV drug resistance testing was performed using the oligonucleotide ligation assay (OLA) on dried blood spots (DBS) collected at enrolment and monthly follow-up visits for 2 years.
South African children who failed HIV-prophylaxis had a high prevalence of NNRTI-resistant HIV (46/88; 52%). Among children with NNRTI-resistance, the frequency of the predominant resistant variant in each child's HIV-quasispecies was high (median 96%) at study entry (median age 7.5 months), and in 26 out of 27 followed a median of 13 months persisted at a high frequency (median 89%).
Our finding that infants who fail HIV-prophylaxis frequently have long-lived NNRTI-resistant HIV suggests that resistance will likely persist through 36 months of age, when children qualify for NNRTI-based ART. These children may benefit from HIV drug resistance testing to guide selection of their treatment.
我们着手研究在一组预防母婴传播(PMTCT)失败的HIV感染儿童中,赋予高水平非核苷类逆转录酶(NNRTI)耐药性的突变的流行情况和持续性。
在南非比勒陀利亚卡拉方省三级医院的儿科HIV诊所进行的一项前瞻性观察队列研究。
2010年7月至2013年2月,纳入开始接受抗逆转录病毒治疗(ART)的儿童。使用寡核苷酸连接测定法(OLA)对入组时及随后2年每月随访采集的干血斑(DBS)进行HIV耐药性检测。
预防HIV失败的南非儿童中,对NNRTI耐药的HIV感染率很高(46/88;52%)。在对NNRTI耐药的儿童中,在研究开始时(中位年龄7.5个月),每个儿童HIV准种中主要耐药变异体的频率很高(中位值96%),并且在27名儿童中的26名中,经过中位13个月的随访,仍以高频率持续存在(中位值89%)。
我们的研究发现,预防HIV失败的婴儿经常携带长期存在的对NNRTI耐药的HIV,这表明耐药性可能会持续到儿童符合基于NNRTI的ART治疗条件的36个月龄。这些儿童可能会从HIV耐药性检测中受益,以指导其治疗选择。