Table 3.

Literature data on the NNRTI effects on gut microbiota in PLWH.

Study Title	Author	Publication Year	Participants	NNRTI Mediated Alpha Diversity Changes	NNRTI Mediated Beta Diversity Changes	NNRTI Mediated Changes in Microbiome Composition	Stool Sample Analysis	NNRTI Mediated Change on Bacterial Translocation or Systematic Inflammation Markers
Impact of Acute HIV Infection and Early Antiretroviral Therapy on the Human Gut Microbiome	Sortino et al. [52]	2020	PLWH before and 6 months after NNRTI treatment vs. seronegative controls	Compared to seronegative controls, alpha diversity was still significantly lower (Chao1, Shannon index)	NNRTI PLWH showed partial restoration	➢Rikenellaceae ↓ ➢Proinflammatory bacteria ↑ ➢Enterobacteriaceae ↑ ➢Bacteroidales ↓ ➢Bacteroidetes ↓ ➢Proteobacteria ↑ ➢Fusobacteria ↑	16S rRNS gene sequencing	➢sCD14 ↓ ➢Fusobacterium was positively associated with sCD14 ➢Polymorphonuclear cell enrichment did not differ after NNRTI ➢Tryptophan levels were restored
Altered Gut Microbiome under Antiretroviral Therapy: Impact of Efavirenz and Zidovudine	Ray et al. [27]	2021	PLWH before and 10 months after NNRTI treatment vs. seronegative controls	Decreased after NNRTI treatment (Fischer, Chao1, ACE)	Only moderate differences could be observed	➢Firmicutes ↑ ➢Bacteriodetes ↓ ➢Prevotellaceae ↓ ➢Lachnospira ↓, Oribacterium ↓, Oscillospira ↓, Prevotella ↓	16S rRNS gene sequencing	-
High microbial translocation limits gut immune recovery during short-term HAART in the area with high prevalence of foodborne infection	Kantamala et al. [15]	2020	PLWH before and 48 weeks after NNRTI treatment	-	-	-	16S rRNS gene sequencing	➢Plasma 16S rDNA unchanged ➢LBP ↓ ➢Gut-homing CD4+ T cell ↑ ➢Th17 cell unchanged ➢sCD14 unchanged ➢I-FABP unchanged
Changes in intestinal microbiota in HIV-1-infected subjects following cART initiation: influence of CD4+ T cell count	Ji et al. [102]	2018	PLWH before and 12 months after NNRTI treatment	PLWH with a baseline of <300/mm3 CD4 T cells had a significant elevation after NNRTI treatment	Significant differences after NNRTI treatment	➢Proteobacteria ↑ ➢Fusobacteria ↑ ➢Bacteroidetes ↓ ➢Ruminococcaceae family ↓ ➢Faecalibacterium genus ↓	16S rRNS gene sequencing	➢I-FABP decreased ➢sCD163 decreased ➢Major alteration only among PLWH with a baseline of <300/mm3 CD4