Chuan Zhang, Yuming Guo, Xiang Xiao, Michael S Bloom, Zhengmin Qian, Craig A Rolling, Hong Xian, Shao Lin, Shanshan Li, Gongbo Chen, Pasi Jalava, Marjut Roponen, Maija-Riitta Hirvonen, Mika Komppula, Ari Leskinen, Steve Hung Lam Yim, Duo-Hong Chen, Huimin Ma, Xiao-Wen Zeng, Li-Wen Hu, Kang-Kang Liu, Bo-Yi Yang, Guang-Hui Dong
Association of Breastfeeding and Air Pollution Exposure With Lung Function in Chinese Children
JAMA network open
randomised comparative data efficacy safety secondline antiretroviral therapy art failure nonnucleoside reverse transcriptase inhibitors nnrtis across diverse geographical settings scarce aim study evaluate optimal secondline art people hiv d2eft completed international randomised openlabel phase 3b4 trial evaluating three secondline art strategies adults aged 18 years hiv1 firstline nnrti therapy failed study done 28 sites across 14 countries asia africa latin america originally designed compare recommended standard care ritonavirboosted darunavir 800 mg darunavir plus 100 mg ritonavir daily plus two nucleoside reverse transcriptase inhibitors nrtis dosed twice daily novel nucleoside sparing regimen dolutegravir 50 mg daily ritonavirboosted darunavir study adapted first year add third arm dolutegravir 50 mg daily fixed tenofovir disoproxil fumarate 300 mg daily plus either lamivudine 300 mg daily emtricitabine 200 mg daily participants randomly assigned computergenerated blocked randomisation scheme block size two stratified site previous tenofovir disoproxil fumarate use hiv viral load trial designed evaluate noninferiority either interventional arm standard care primary outcome virological suppression determined hiv rna load less 50 copies per ml 48 weeks prespecified noninferiority margin 12 comparisons made modified intentiontotreat population including participants randomly assigned excluding administrative withdrawals study registered clinicaltrialsgov nct03017872 1190 individuals screened 828 participants enrolled nov 1 2017 dec 31 2021 two participants unable receive assigned regimen administrative reasons 826 participants included analyses median age 39 years iqr 3346 450 54 participants female baseline median cd4 count 206 cells per l 23354 median hiv rna 15 400 copies per ml 360065 986 proportion participants hiv rna less 50 copies per ml 48 weeks 194 75 257 ritonavirboosted darunavir plus two nrtis group 222 84 264 ritonavirboosted darunavir plus dolutegravir group 227 78 291 dolutegravir tenofovir disoproxil fumarate plus either lamivudine emtricitabine group compared ritonavirboosted darunavir plus two nrtis difference virological suppression 86 95 ci 17 155 p0016 dolutegravir plus ritonavirboosted darunavir 67 12 144 p0093 dolutegravir tenofovir disoproxil fumarate plus either lamivudine emtricitabine six deaths occurred none related treatment 19 pregnancies 11 livebirths occurred congenital defects individuals experiencing failure nnrtibased firstline art switch either dolutegravir plus ritonavirboosted darunavir dolutegravir tenofovir disoproxil fumarate plus either lamivudine emtricitabine without universal access genotyping noninferior achieving viral suppression compared ritonavirboosted darunavir plus two nrtis global data support recent treatment guidelines unitaid national institute allergy infectious diseases usa national health medical research council australia viiv healthcare janssen