Search

Table S1. Study participant’s flow and samples available for testing. Figure S1. Diagram of study design with the prospective longitudinal and the cross-sectional components. Figure S2. Longitudinal evolution of CD4+ and CD8+ T cell counts and HIV-1 RNA levels. Figure S3. Changes in observed richness and Shannon’s diversity using shotgun sequencing. Figure S4. Ordination plot of cross-sectional sample dataset using gut microbiota composition. Figure S5. Beta-diversity of the fecal microbiomes during the first (RHI < 6) and second 6 months (RHI > 6) following HIV-1 infection. Figure S6. Evolution of reactive oxygen species (ROS)-associated enzymes in recently HIV-1-infected vs. HIV-1-negative subjects. Figure S7. Differences in bacterial genera relative abundance between adenovirus-, cytomegalovirus- and enterovirus-positive and -negative groups using LEfSe. Figure S8. Cytokines and immune measurements in blood and feces differentially abundant between adenovirus, enterovirus, and cytomegalovirus-positive and -negative groups. (DOCX 2327 kb)

Background: Monotherapy with ritonavir-boosted PIs (PI/r) has been used to simplify treatment of HIV-1-infected patients. In previous studies raltegravir intensification evidenced ongoing viral replication and reduced T cell activation, preferentially in subjects receiving PI-based triple ART. However, data about low-level viral replication and its consequences in patients receiving PI/r monotherapy are scarce. Methods: We evaluated the impact of 24 weeks of intensification with raltegravir on markers of viral persistence, cellular immune activation and inflammation biomarkers in 33 patients receiving maintenance PI/r monotherapy with darunavir or lopinavir boosted with ritonavir. ClinicalTrials. gov identifier: NCT01480713. Results: The addition of raltegravir to PI/r monotherapy resulted in a transient increase in 2-LTR (long-terminal repeat) circles in a significant proportion of participants, along with decreases in CD8+ T cell activation levels and a temporary increase in the expression of the exhaustion marker CTLA-4 in peripheral T lymphocytes. Intensification with raltegravir also reduced the number of samples with intermediate levels of residual viraemia (10-60 HIV-1 RNA copies/mL) compared with samples taken during PI/r monotherapy. However, there were no changes in cell-associated HIV-1 DNA in peripheral CD4+ T cells or soluble inflammatory biomarkers (CD14, IP-10, IL-6, C-reactive protein and D-dimer). Conclusions: Intensification of PI/r monotherapy with raltegravir revealed persistent low-level viral replication and reduced residual viraemia in some patients during long-termPI/r monotherapy. The concomitant change in T cell phenotype suggests an association between active viral production and T cell activation. These results contribute to understanding the lower efficacy rates of PI/r monotherapies compared with triple therapies in clinical trials.