ABSTRACT
BACKGROUND: Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI) with an increased genetic barrier to resistance with respect to raltegravir (RAL) or elvitegravir (EVG). Few data are available on the durability of DTG-containing regimens. OBJECTIVES: We aimed at investigating the duration of the DTG-containing regimen, the occurrence of an HIV-1 RNA blip, and factors associated with DTG virological response. STUDY DESIGN: From the Antiviral Response Cohort Analysis database, we selected 89 HIV-1-positive four-class-experienced subjects who started DTG after receiving RAL or EVG. Factors associated with durability and virological response were analysed by logistic regression. RESULTS: After a median duration of 18.8 [0.4-76.2] months, 79/89 (88.8%) subjects were still on DTG. All subjects remaining on DTG at the end of follow-up had undetectable HIV-1 RNA, compared to 5/10 subjects who discontinued DTG. DTG discontinuation was less frequent in patients who had experienced ≥10 regimens (HR 0.11, pâ¯=â¯0.040). The probability of having an HIV-1 RNA positive value at the last follow-up significantly increased in patients with non-B HIV-1 subtype (HR 5.77, pâ¯<â¯.001) and significantly decreased in patients with CD4 nadir >200/µL (HR 0.29, pâ¯=â¯0.038), with more than 10 previous regimens (HR 0.27, pâ¯=â¯0.040), and who harbored virus with IN mutations (HR 0.12, pâ¯=â¯0.023) at DTG start. CONCLUSIONS: After previous exposure to first-generation INIs, treatment with DTG showed long durability and did not show virological rebound after virological suppression. Subjects infected with a non-B HIV-1 subtype had a greater risk of having detectable HIV-1 RNA at the last observation.
Subject(s)
Anti-HIV Agents/therapeutic use , Drug Resistance, Multiple, Viral , HIV Infections/drug therapy , Heterocyclic Compounds, 3-Ring/therapeutic use , Quinolones/therapeutic use , Raltegravir Potassium/therapeutic use , Sustained Virologic Response , Adult , Anti-HIV Agents/administration & dosage , Cohort Studies , Female , HIV Infections/epidemiology , HIV-1/drug effects , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , Male , Middle Aged , Oxazines , Piperazines , Pyridones , Quinolones/administration & dosage , RNA, Viral/blood , Raltegravir Potassium/administration & dosage , Retrospective Studies , Young AdultABSTRACT
Pharmacokinetic and pharmacodynamic endpoints of intravenously and orally administered docetaxel (DT) with or without oral cyclosporine were characterized in rats and dogs. Plasma samples were analysed for DT using liquid chromatography-mass spectrometry. DT area-under-the-concentration-time curve, plasma clearance and maximum serum clearance were significantly affected by cyclosporine in rats (P
ABSTRACT
La utilidad esencial del LEEP sobre el cuello uterino el SIl de alto grado, cuando se cumplen ciertas condiciones: lesión no mayor de dos cuadrantes, canal endocervical libre, posibilidad de seguimiento y, para algunos autores, deseos de paridad. Utilizamos el equipo Cooper Surgical LEEP system 6000, anestesándose el cuello uterino en cada cuadrante