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| Author | Method | Year of publication | Primary endpoint | Number of patients | Conclusion |
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| Barrios et al. [92] | Retrospective cohort study | 2005 | HIV-infected individuals who initiated a protease inhibitor-sparing regimen were retrospectively assessed by analyzing viral load and CD4+ count. | 570 | Patients receiving ddI + TDF-based combinations showed a decrease in CD4+ count despite having an undetectable viral load. |
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| Gandhi et al. [79] | Prospective, randomized, placebo- controlled trial | 2010 | Groups were randomized with RAL intensification or placebo, and plasma HIV-1 RNA was averaged between weeks 10 and 12. | 53 | 12 weeks of RAL intensification did not demonstrably reduce low-level plasma viremia in patients on currently recommended cART. |
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| Hatano et al. [81] | Prospective, randomized, placebo- controlled trial | 2011 | Patients received 24 weeks of cART intensification with RAL or placebo. End points were defined as change in the % CD38+HLA-DR+CD8+ T-cells in PBMCs and number of patients with undetectable viral load. | 30 | RAL intensification did not have a significant effect on immune activation or HIV-specific responses in PBMCs or gut-associated lymphoid tissue. |
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| Chege et al. [76] | Prospective, randomized, placebo- controlled trial | 2012 | Patients received 48 weeks of cART intensification with RAL or placebo. After week 48, all patients were given RAL until week 96. Blood and sigmoid biopsies were sampled to document CD4+ count as well as HIV-1 proviral DNA load. | 24 | RAL did not cause any significant difference in CD4+ count and blood and gut HIV-1 proviral load compared to placebo. |
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| Martínez et al. [82] | Prospective, randomized, open-label study | 2012 | Changes in fasting lipids, hsCRP, MCP-1, osteoprotegerin, IL-6, IL-10, TNF-α, ICAM-1, VCAM-1, E-selectin, P-selectin, adiponectin, insulin, and D-dimer were documented for 48 weeks in patients on a RAL-boosted protease inhibitor and those who were switched to RAL. | 273 | Significant decreases in cardiovascular biomarkers were reported in patients who were switched to RAL. |
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| Cuzin et al. [86] | Prospective, open-label study | 2012 | Patients were put on MVC intensification and changes in CD4+ slopes were documented. | 60 | MVC intensification caused enhancement of CD4+ cell slopes in patients with history of poor immune restoration. |
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| Silva et al. [83] | Prospective, randomized, open-label study | 2013 | Plasma IL-6, hsCRP, and D-dimer levels were documented at baseline and at weeks 24 and 48. | 164 | At week 24, a significant decrease in IL-6 and D-dimer level was seen in the immediate RAL switch arm compared with the deferred switch arm. At week 48, the deferred RAL switch arm had a decrease in all measured biomarkers. |
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| Gupta et al. [85] | Prospective, randomized, placebo- controlled trial | 2013 | Flow-mediated dilation, 25(OH) vitamin D, PTH levels, total cholesterol, hsCRP, serum ALP, sCD14 levels, and renal function were compared for 24 weeks between patients on EFV and those switched to RAL. | 30 | The RAL switch group showed a decrease in total cholesterol, hsCRP, serum ALP, sCD14 levels, and renal function. |
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| Hunt et al. [87] | Prospective, randomized, placebo- controlled trial | 2013 | Patients with MVC intensification were compared to a placebo group by measuring % CD38+HLA-DR+, CD8+, CD4+, CCR5 ligand levels, plasma lipopolysaccharide, sCD14 levels, and neutrophils. | 45 | During MVC intensification, plasma lipopolysaccharide declined and sCD14 and neutrophils increased in blood and rectal tissue. |
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| Hatano et al. [80] | Prospective, randomized, placebo- controlled trial | 2013 | Patients received 24 weeks of cART intensification with RAL or placebo. 2-LTR circles by droplet digital polymerase chain reaction were documented at weeks 0, 1, 2, and 8. | 31 | RAL intensification resulted in a rapid increase in the level of 2-LTR circles in a proportion of subjects, indicating that low-level viral replication persists in some individuals even after long-term cART. |
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| Lake et al. [84] | Prospective, randomized open-label study | 2014 | Changes in sCD14 and other inflammatory biomarkers in virologically suppressed HIV-infected women were documented for 48 weeks. | 37 | A switch to RAL from a protease inhibitor or nonnucleoside reverse transcriptase inhibitor was associated with a statistically significant decline in sCD14. |
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| Papakonstantinou et al. [91] | Prospective, open-label study | 2014 | Treatment naïve patients were assigned a regimen of TDF/FTC/EFV or ABC/3TC/EFV. Inflammatory markers, metabolic enzymes, and HIV-implicated cytokines were collected and compared for a 12-month period. | 18 | The TDF-containing regimen caused a decrease in PAF levels and Lp-PLA2. The ABC-containing regimen caused increased Lp-PLA2. |
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| Hileman et al. [89] | Prospective, randomized, double-blinded study | 2015 | sCD14, sCD163, sTNF-RI, IL-6, hsCRP, and Lp-PLA2 were compared over 24 and 48 weeks between patients on EVG and EFV. | 200 | EVG seems to have better effects on immune activation than EFV. |
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| Belaunzarán-Zamudio et al. [88] | Prospective, randomized, placebo- controlled trial | 2016 | Flow cytometry was used to characterize the maturation phenotype, CCR5 ligand level expression, and T-cell activation at weeks 0, 4, 12, 24, and 48 in patients who received MVC intensification. CD4+ and CD8+ cell reactivity was also determined by intracellular expression of IFN-γ, TNF-α, and CD40 ligand at weeks 0, 4, and 12. | 40 | Those on MVC intensification retained CD4+ and CD8+ cells. Treatment had no effect on the occurrence of IRIS. |
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| Chan et al. [90] | Prospective, randomized, double-blinded study | 2016 | 32 biomarkers and bone mineral density of the hip were measured at weeks 0 and 48 for treatment naïve patients on MVC or TDF. | 230 | Initiating cART with MVC compared to TDF caused a greater increase in CD4+ count and smaller decline in CD8+ count, but less rise in CD4+/CD8+ ratio. There was no difference in inflammatory biomarkers. |
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