Drug resistance among newly diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis

Abstract

Background In the era of more efficacious prevention of mother-to-child transmission (PMTCT) regimens, documenting the profile of drug resistance in HIV-infected infants and young children is critical to our efforts to improve care and treatment for children. Methods HIV drug resistance mutations in plasma virus were ascertained using population sequencing among 230 newly-diagnosed HIV-infected children under 2 years of age recruited in Johannesburg, South Africa, during 2011. By this time, more effective PMTCT regimens, including combination antiretroviral therapy (cART) for pregnant women, were being implemented. Results Two-thirds (67.4%) of HIV-infected children had been exposed to some form of maternal (89%) and/or infant (97%) PMTCT. Among PMTCT-exposed, 56.8% had non-nucleoside reverse transcriptase inhibitor (NNRTI), 14.8% nucleoside reverse transcriptase inhibitor (NRTI), and 1.3% protease inhibitor (PI) mutations. NNRTI mutations were strongly related to younger age. The remaining third (32.6%) had no reported or recorded PMTCT exposures but resistance to NNRTI was detected in 24.0%, NRTI in 10.7% and PI in 1.3%. Conclusion The new PMTCT strategies dramatically reduce the number of children who acquire infection but among those who do become infected, NNRTI resistance prevalence is high. In this South African setting with high PMTCT coverage, almost a quarter of children with no reported or recorded PMTCT also have drug resistance mutations. PMTCT history is an inadequate means of ruling out pre-treatment drug resistance. Our results support the use of PI-based first-line regimens in HIV-infected infants and young children regardless of PMTCT history.

Antiretroviral Treatment and Resistance Patterns in HIV-Infected Children

“…Onethird of the children had no exposure to PMTCT. However, 24.0 % were detected to have resistance to NNRTI, NRTI in 10.7 % and PI in 1.3 % [27]. Shao et al [28] carried out a study to determine DRM among children under 18 months born to HIV-1-infected mothers who accessed PMTCT services in northern Tanzania.…”

“…This is also consistent with the evidence that knowledge of patient's virus resistance profile prior to treatment will go a long way to avoid unnecessary stopping of a particular regimen and switching to others regimens. The cohorts showed resistance across the main ARV classes although in varying degrees [15,18,22,[24][25][26][27][28][29][30][31].…”

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

“…New pediatric HIV infections have declined dramatically; however, children who acquire HIV often do so while exposed to antiretroviral drugs. The development of antiretroviral drug resistance with failed PMTCT is well documented in the setting of "single-dose" nevirapine (NVP) for PMTCT [5][6][7]; however, similar complications may occur with continuous infant nevirapine prophylaxis or maternal ART [8][9][10]. Ongoing work is needed to optimize pediatric ART, to ensure that the regimens offered are effective and durable over time.…”

HIV-1 Subtype Diversity and Prevalence of Primary Drug Resistance in a Single-Center Pediatric Cohort in Germany

“…A recently published prospective observational study from South Africa demonstrated a high prevalence of NNRTI resistance (52%) among infants who fail HIV-prophylaxis [29]. In another study from South Africa conducted in 2011, 56.8% of HIV-1-infected children harbored NNRTI, 14.8% harbored NRTI, and 1.3% harbored PI mutations [3]. Since a relevant percentage of new HIV-1-infected children seen at our center are immigrants from sub-Saharan Africa, this selection of DRMs being reported might have an impact on the prevalence of DRMs in the future.…”

“…The use of ART in pregnancy and as prophylaxis in infants for the prevention of mother-to-child transmission (MTCT) has led to a pronounced reduction of vertical HIV-1 transmission, but a selection of drug-resistant mutations (DRMs) in infected infants is increasingly being reported [3,4]. Some HIV-1 subtypes and recombinants seem to accelerate the emergence of DRMs [4,5].…”