Patient characteristics at the initiation of NVP plus TDF plus FTC (or 3TC) as a switch strategy (n = 341).

<p>Data are median (IQR) or n (%).</p><p>* Some individuals in the early calendar years had an undetectable viral load at baseline, but with tests using at that moment a threshold of 80 or 200 copies/mL.</p><p>MSM: Men having sex with men; NRTI: Nucleos(t)ide reverse transcriptase inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; PI: Protease inhibitor.</p><p>Patient characteristics at the initiation of NVP plus TDF plus FTC (or 3TC) as a switch strategy (n = 341).</p

Time to virological failure and treatment failure through the long term follow-up.

<p>Virological failure was defined as two consecutive measurements of pVL >50 copies/mL. Treatment failure included subjects with virological failure, treatment discontinuations due to drug toxicity, and death.</p

Mutations shown at failure in the reverse transcriptase and protease, and NRTI included in the regimen together with NVP and TDF (3TC vs FTC).

<p>Mutations shown at failure in the reverse transcriptase and protease, and NRTI included in the regimen together with NVP and TDF (3TC vs FTC).</p

Factors associated with virologic failure to a switch regimen composed of NVP plus TDF plus FTC (or 3TC) (n = 341).

<p>* Some individuals in early calendar years had an undetectable viral load at baseline, but with tests using a threshold of 80 or 200 copies/mL.</p><p>VL: viral load; VF: virologic failures; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTI: nucleoside analogue reverse transcriptase inhibitor; PI: protease inhibitor.</p><p>Factors associated with virologic failure to a switch regimen composed of NVP plus TDF plus FTC (or 3TC) (n = 341).</p

Additional file 1: of Increased ex vivo cell death of central memory CD4 T cells in treated HIV infected individuals with unsatisfactory immune recovery

Figure S1. Gating strategy followed to identify T-cell maturation stages. Panel A. CD4 and CD8 T cells were gated and analyzed for the expression of CD27 and CD28. For CD4 T cells, terminally differentiated (TTD) cells were defined as CD28–CD27−, while effector memory (TEM) cells were CD28+CD27−. Double positive cells were further analyzed for CCR7 and CD45RA expression to identify naïve (TN) cells (CCR7+CD45RA+), central memory (TCM) cells (CCR7+CD45RA−) and transitional Memory (TTM) cells (CCR7–CD45RA−). Panel B. For CD8 T cells, the general strategy was similar, unless for the definition of TEM cells that was CD27+CD28– cells. The expression of CD57 was analyzed in the whole CD4 or CD8 T-cell population (lower left dot plot in each panel) to define replicative senescence (CD28–CD57+ cells). In addition the expression of CD57 in each subset was also evaluated (lower dot plots in each panels)

Additional file 3: of Increased ex vivo cell death of central memory CD4 T cells in treated HIV infected individuals with unsatisfactory immune recovery

Figure S2. A model for CD4 homeostasis in Immunodiscordant individuals. Immunoconcordant individuals show a full recovery of CD4 T-cell counts with a high representation of naïve cells, and balanced frequencies of different memory subsets (upper panels). The profile of CD4 T-cell maturation in immunoconcordant individuals (green line) overlaps with that of HIV uninfected individuals (blue line in upper right plot) in which CCR7− CD4 T cells show increased turnover and short live [22]. Conversely,immunodiscordant individuals (lower panels) show a reduced naïve subset with no signs of altered turnover [14] that limits the generation of new memory cells. Among memory subsets, central memory cells are also reduced and subjected to homeostatic pressure to generate new cells [14] increasing TCM→TTM transition (and lowering TCM/TTM ratios) and increasing TCM cell death. TTM and TEM cells emerging from TCM cells also show higher sensitivity to cell death (Figure 2D), explaining the lack of accumulation of terminally differentiated cells in these subjects. This scenario results in a shifted profile of CD4 T-cell maturation (red line) compared to healthy individuals (blue line in lower right plot)

Changes in lipid profile and glycemia and satisfaction.

<p>All values are shown as mean (SD).</p>*<p>P values express intra-group differences between baseline and week 48.</p><p>Between groups, the only differences recorded were for triglycerides (p = 0.04) and glycemia (p = 0.03) at week 24.</p><p>HDL, High density lipoprotein; LDL, Low density lipoprotein.</p>**<p>Patient satisfaction was assessed using two 0–10 likert scales.</p

Baseline epidemiological and HIV-related characteristics.

<p>Parameters are expressed as Median value (IQR 25;75) except when it was specified. HCV, hepatitis C virus; HBV, hepatitis B virus; PI, protease inhibitors; NNRTI, non-nucleoside analog reverse transcriptase inhibitor; RTV, ritonavir; BID, twice daily dosin.</p

Time of progression.

<p>Time of progression from normal bone mineral density to osteopenia overall (n = 112 patients) (A) and after stratification according to minimum baseline T score (“low-risk", “middle-risk", and “high-risk") (B).</p

Time of progression to osteoporosis.

<p>Time of progression from osteopenia to osteoporosis overall (n = 211 patients) (A) and after stratification by baseline minimum T score (“low-risk", “middle-risk", and “high-risk") (B).</p