RESUMO
OBJECTIVES: To assess the risk of adverse diagnoses and laboratory abnormalities associated with a 300 or 150âmg daily dose of lamivudine (3TC) initiated by people with HIV (PWH) with an estimated glomerular filtration rate (eGFR) between at least 30 and 49âml/min perâ1.73 m2 or less. DESIGN: Longitudinal study based on electronic health records of 539 PWH with eGFR between at least 30 and 49âml/min perâ1.73 m2 or less from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. METHODS: Common unintended effects of 3TC were evaluated as composite outcomes. We estimated the incidence (univariate Poisson regression) and association between dose and incident composite outcomes (multivariate Poisson regression) among PWH without the relevant diagnoses or laboratory abnormalities at 3TC initiation. RESULTS: PWH initiating 150âmg 3TC had higher HIV RNA, lower eGFR, and more comorbidities than those initiating 300âmg 3TC. The prevalence of relevant diagnoses and laboratory abnormalities was similar in both groups. The most common lab abnormality was low hemoglobin. There was no statistically significant difference in incident adverse diagnoses/severe lab abnormalities with 300âmg versus 150âmg [incidence rate ratio (IRR): 1.51; 95% confidence interval (CI) 0.59--3.92). However, a statistically significant association was observed when gastrointestinal symptoms/moderate lab abnormalities were included in the outcome (IRR: 3.07, 95% CI 1.12--8.40). CONCLUSION: As 3TC is a well tolerated drug with a wide therapeutic window, dose adjustment may be unnecessary among PWH with eGFR between at least 30 and 49âml/min per 1.73 m2 or less. Clinical judgement is key when weighing the risks and benefits of 3TC dose adjustment for PWH experiencing gastrointestinal symptoms or moderate lab abnormalities.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Rim , Lamivudina/efeitos adversos , Estudos LongitudinaisRESUMO
OBJECTIVE: To assess the use of two-drug antiretroviral regimens (2DR) and virologic and immunologic outcomes compared with three-drug regimens (3DR) in the EuroSIDA cohort. DESIGN: Multicentre, prospective cohort study. METHODS: Logistic regression was used to analyse the uptake and outcomes among HIV-positive individuals who started or switched to a 2DR compared with those on a 3DR. Virologic outcomes were assessed on-treatment as the proportion of individuals with controlled viral load (<400âcopies/ml), or with a composite modified FDA snapshot endpoint (mFDA), with mFDA success defined as controlled viral load at 6 months or 12 months for individuals with a known viral load, no regimen changes, AIDS or death. Immunologic response was defined as a 100âcells/µl or a 25% increase in CD4 cell counts from baseline. RESULTS: Between 1 July 2010 and 31 December 2016, 423 individuals started or switched to a 2DR (eight antiretroviral-naive) and 4347 started a 3DR (566 naive). Individuals on 2DR tended to have suppressed viral load, higher CD4 cell counts and more comorbidities at baseline compared with those on 3DR. There were no differences in the proportions of individuals who obtained on-treatment or mFDA success, and no significant differences in the adjusted odds ratios for mFDA success or immunologic responses between the 2DR and 3DR groups at 6 months or 12 months. CONCLUSION: In routine clinical practice, 2DR were largely used for virologically suppressed individuals with higher cumulative exposure to antiretrovirals and comorbidities. Virologic and immunologic outcomes were similar among those on 2DR or 3DR, although confounding by indication cannot be fully excluded due to the observational nature of the study.