Information on the virologic durability of modern antiretroviral regimens is important to clinicians. We aimed to describe virologic durability of first-line integrase strand transfer inhibitor (INSTI)-, nonnucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based antiretroviral regimens. This was a retrospective study of antiretroviral-naïve patients that initiated first-line antiretroviral regimens with two nucleoside reverse transcriptase inhibitors and an INSTI, NNRTI, or PI between January 2006 and June 2016. The outcome was time to virologic failure, which was assessed by Kaplan–Meier survival analysis and Cox regression models. There were 780 patients (median age = 37 years [interquartile range (IQR) = 30–45], 93.3% male, 56.2% Caucasian, median HIV duration = 1.8 years [IQR = 0.4–5.4], baseline log10 viral load [VL]=4.6 [IQR = 4.1–5.1], and baseline CD4+ cell count = 320 cells/µl [IQR = 217–440]). In total, 189/780 were on a third agent INSTI, 339/780 on a third agent NNRTI, and 252/780 on a third agent PI. Kaplan–Meier survival probability revealed longer time to virologic failure for INSTI, followed by NNRTI then PI (p < 0.001). Multivariable Cox regression revealed that being on an INSTI regimen (aHR = 0.27; 95%CI = 0.18–0.41) or NNRTI regimen (aHR = 0.64; 95%CI = 0.47–0.87) versus PI regimen, frequent VL testing (per year), (aHR = 0.64; 95%CI = 0.47–0.87), and duration of ART (aHR = 0.22; 95%CI = 0.17–0.30) (years) were inversely associated with time to virologic failure, and log10 of baseline VL (aHR = 1.94; 95%CI = 1.58–2.39 per log10) increased risk. Virologic failure was delayed and virologic durability prolonged for INSTI- compared to NNRTI- and PI-based regimens, supporting current antiretroviral therapy guidelines.
IntroductionThe resistance profiles of first-line antiretroviral therapy (ART) regimens after virologic failure have yet to be studied in a clinic setting in the modern treatment era. Time to virologic failure among three standard first-line regimens and the resistance profiles of these failures were compared.Materials and MethodsAll HIV-positive persons aged 16 and over starting a three-drug first-line ART regimen were retrospectively identified at a Toronto community clinic (1 January 2006–1 January 2013). The regimens included a backbone of two NRTIs and a third agent; a PI, an NNRTI, or an II. Patients must have been on treatment for at least 14 days and have at least one VL test within 6 months after starting treatment. The primary outcome was virologic failure defined as either: no suppression by 6 months, or after suppression, two consecutive, detectable VL200 copies/mL at least 14 days apart or one VL>200 copies/mL. Time to failure was compared using a proportional hazards model adjusting for demographic and clinical factors. Resistance profiles of NRTIs and third agents are described in patients with virologic failure who had both baseline and virologic failure genotypes.ResultsSix hundred sixty patients (93% male) were included with a mean age of 38.9 and a median follow-up period of 35.3 (32.2–39.3) months. Distribution of third agent use was: PI 37.3% (n=246), NNRTI 55.9% (n=369) and II 6.8% (n=45). Virologic failures occurred in 81/246 (33%) with PI, 87/369 (24%) with NNRTI and 11/45 (24%) with II. Compare to PIs, time to failure was longer with NNRTIs (p=0.0013) and similar for IIs (p=0.1562). No evidence that failure with NNRTIs was different from IIs (p=0.9139). Of the 660 patients, 567 (86%) had a baseline genotype. Of the 567 patients, 179 had virological failure. Of the 179, 145(81%) had a baseline genotype and only 37 (21%) had both a baseline and follow-up genotype. Upon failure, emerging ART resistance was rare. No new PI or II mutations were identified and one new NNRTI (Y181C) mutation was identified. Three patients taking PI-based regimens developed NRTI mutations (M184V, M184I, T215Y).ConclusionsTime to virologic failure was significantly greater in the NNRTI group compared to the PI group. If failure did occur, ART resistance rarely developed with no PI mutations but a few NRTI mutations in those taking PI-based regimens, and NNRTI mutations in those taking NNRTI-based regimen.
The purpose of the literature review was to conduct a general analysis of the literature data on the study of comorbidity between coronavirus disease and inflammatory periodontal diseases. Studies have found that periodontitis is significantly associated with a higher risk of complications from COVID-19, including intensive care unit hospitalization, the need for assisted ventilation and death, as well as increased blood levels of markers associated with worse COVID-19 outcome. 19, such as D-dimer, serum leukocyte level and CRP concentration. The article describes the mechanisms of penetration of the SARS-CoV-2 virus into the human body, the common links of pathogenesis between COVID-19 and periodontitis, the importance of oral hygiene for patients with COVID-19, and considers the clinical and general immunological aspects of inflammation in COVID-19 and periodontitis. Currently, most research is focused on whether the presence of periodontal disease affects the outcome of coronavirus disease. The possibility of cross-talk between SARS-CoV-2 and the oral microbiome, which may affect the subsequent course of periodontitis at the post-covid stage, presents the scientific interest.
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