Discontinuation of Initial Antiretroviral Therapy in Clinical Practice: Moving Toward Individualized Therapy.

Background: Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years. Methods: Patients who initiated first cART between January 2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan–Meier analysis was used for the outcome discontinuation of >=1 drug regardless of the reason. Cox regression analysis wasused to identify factors associated with treatment discontinuation because of the 3 reasons considered. Results: A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4+ cell (P = 0.011), and higher lymphocyte T CD8+ cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044). Conclusions: In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity

Exposure to abacavir and biomarkers of cardiovascular disease in HIV-1-infected patients on suppressive antiretroviral therapy: a longitudinal study

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Uptake and discontinuation of integrase inhibitors (INSTIs) in a large cohort setting.

BACKGROUND Despite increased INSTI use, limited large-scale, real-life data exists on INSTI uptake and discontinuation. SETTING International multicohort collaboration. METHODS RESPOND participants starting dolutegravir (DTG), elvitegravir (EVG) or raltegravir (RAL) after 1/1/2012 were included. Predictors of INSTI used were assessed using multinomial logistic regression. Kaplan Meier and Cox proportional hazards models describe time to and factors associated with discontinuation. RESULTS Overall, 9702 persons were included; 5051 (52.1%) starting DTG, 1933 (19.9%) EVG, 2718 (28.0%) RAL. The likelihood of starting RAL or EVG versus DTG decreased over time and was higher in Eastern and Southern Europe compared to Western Europe.At 6 months after initiation, 8.9% (95% CI 8.3%-9.5%) had discontinued the INSTI (6.4% DTG, 7.4% EVG, 14.0% RAL). The main reason for discontinuation was toxicity (44.2% DTG, 42.5% EVG, 17.3% RAL). Nervous system toxicity accounted for a higher proportion of toxicity discontinuations on DTG (31.8% DTG, 23.4% EVG, 6.6% RAL). Overall, treatment simplification was highest on RAL (2.7% DTG, 1.6% EVG, 19.8% RAL).Factors associated with a higher discontinuation risk included increasing year of INSTI initiation, female gender, hepatitis C coinfection, and prior non-AIDS defining malignancies. Individuals in Southern and Eastern Europe were less likely to discontinue. Similar results were seen for discontinuations after 6 months. CONCLUSION Uptake of DTG versus EVG or RAL increased over time. Discontinuation within 6 months was mainly due to toxicity; nervous system toxicity was highest on DTG. Discontinuation was highest on RAL, mainly due to treatment simplification

Viral Interference Between Hepatitis B, C, and D Viruses in Dual and Triple Infections in HIV-Positive Patients

Objective: To investigate the reciprocal inhibitory effects of hepatitis B virus (HBV)/hepatitis C virus (HCV)/hepatitis D virus (HDV) infections in naive and previously antiretroviral-experienced HIV-positive patients. Design: This retrospective Study involved 72 consecutive patients of the Italian Cohort Naive Antiretroviral cohort: 21 coinfected with HBV/HCV (group IBC), 18 infected with HBV (group 2B), and 33 infected with HCV (group 3C). Methods: Viral interference between HBV and HCV was assessed by means of the qualitative detection, quantification, and genotyping of each virus; HDV infection was assessed by means of genomic amplification. Results: Univariate analysis showed that HBV DNA was less frequently detected in group I BC than in group 213 (16 of 21 vs 18 of 18; P = 0.02), their HBV load was significantly lower (median 3.9 vs 5.4 log(10) HBV DNA copies/mL; P = 0.002), and they more frequently carried HBV genotype D (12 of 13 vs 4 of 11; P = 0.0071). HCV RNA was less frequently detected in group I BC than in group 3C (12 of 21 vs 33 of 33; P 0.0001), and HDV RNA was more frequently detected in group IBC than in group 213 (9 of 21 vs 2 of 18; P = 0.028). Multivariate analysis of the, HBV-infected subjects showed that the risk of HCV coinfection was associated with older age [relative risk 0.28, 95% confidence interval (CI): 0.09 to 0.90; P = 0.033 for every 10 years older] and intravenous drug use (relative risk 73, 95% CI: 2.4 to >999.999; P = 0.013). The only predictor of HBV coinfection in HCV-infected individuals was a lower HCV load (relative risk 0.30, 95% CI: 0.11 to 0.79 for every additional log(10) HCV RNA; P = 0.015). Conclusion: HBV and HCV showed alternative dominant replication in the I.Co.N.A. cohort, with HBV having a more unfavorable effect on HCV replication