Chemical structures of the studied non-nucleoside reverse transcriptase inhibitors.

<p>Chemical structures of the studied non-nucleoside reverse transcriptase inhibitors.</p

Effect of EFV, NVP and RPV on the survival fraction of cancer cells.

<p>Colony formation assays were performed with (a) EFV, (b) NVP and (c) RPV. The pancreatic cancer cell line BxPC-3 was treated for 72h with each of the drugs. The survival fraction (SF) was analyzed and normalized to the control. Graphs were fitted and the EC50 was calculated.</p

Comparison of blood levels in patients with in vitro toxic EC50 of EFV, NVP and RPV.

<p>Blood levels of (a) EFV, (b) NVP and (c) RPV determined by HPLC (bars). These in vivo concentrations are compared to the fitted function of the in vitro toxicity against BxPC-3 pancreatic cancer cells in the Annexin-V-APC/AAD staining (solid line).</p

Apoptosis and necrosis induction in cancer cells by non-nucleoside reverse transcriptase inhibitors.

<p>The fraction of apoptotic and necrotic cells after treatment with different NNRTIs in different concentrations was measured by Annexin-V-APC/7AAD staining and flow cytometry. An example of the gating in the FACS plots is shown for untreated (a) and with a toxic concentration of EFV treated cells (b). A curve was fitted through the data points of the total fraction of dead cells and the EC50 was calculated for each drug. The pancreatic cancer cell line BxPC-3 was treated for 72h with (c) EFV, (d) NVP, (e) RPV, (f) ETR, (g) LSV and (h) DLV. The pancreatic cancer cell line Panc-1 was treated for 72h with (j) EFV, (k) NVP and (l) RPV.</p

Inter-individual variability for Efavirenz and Nevirapine among 152 participants.

*<p>SD = Standard Deviation</p

Comparison of distribution of patients' characteristics within plasma antiretroviral drug concentrations (sub-therapeutic, therapeutic and supra-therapeutic) among 152 participants.

*<p>NRTI = Nucleoside reverse transcriptase inhibitor, ARV = Antiretroviral; BMI = Body Mass Index; AZT = Azidothymidine (Zidovudine); 3TC = Lamivudine; TDF = Tenofovir; FTC = Emitricitabine; D4T = Stavudine.</p

Demographics and D-dimer levels.

<p>(a) SMART/ESPRIT/SILCAAT; adjusted for demographics, HIV-specific variables and biomarkers of inflammation. (b) SMART/ESPRIT; as in (a) and also adjusted for co-morbidities (CVD, DM and hepatitis B/C) and eGFR. (c) SMART only; as in (b) and also adjusted for smoking, cystatin C and cholesterol levels.</p

Baseline Characteristics by Dataset ESPRIT, SILCAAT and SMART Patients.

<p>*Not ascertained for patients in SILCAAT.</p><p>**Not ascertained for patients in SILCAAT or ESPRIT.</p><p>***Data available for n = 245 participants.</p><p>****Data available for n = 860 participants.</p

Figure 2. D-dimer levels across age groups stratified by gender (a).

<p>(a) SMART/ESPRIT/SILCAAT; adjusted for demographics, HIV-specific variables and biomarkers of inflammation.</p

HIV-specific variables and D-dimer levels.

<p>(a) SMART/ESPRIT/SILCAAT (N = 9848; 821 of whom were off ART at baseline); adjusted for demographics, HIV-specific variables and biomarkers of inflammation. (b) SMART/ESPRIT (N = 6928); as in (a) and also adjusted for co-morbidities (CVD, DM and hepatitis B/C) and eGFR<b>.</b> (c) SMART (N = 4488); as in (b) and also adjusted for smoking, cystatin C and cholesterol levels.</p