The frequency and reasons for antiretroviral switching with specific antiretroviral associations: The SWITCH study

ArticleinAntiviral research 86(2):227-9 · March 2010with12 Reads
DOI: 10.1016/j.antiviral.2010.03.001 · Source: PubMed
We investigated the reasons for switching antiretroviral regimens, an issue rarely addressed in cohort studies. An observed toxicity switch rate (OTSR) was calculated by Poisson regression using the number of days individuals received each individual antiretroviral drug. Of 3333 individuals receiving HAART, a total of 14% of regimens were switched, the majority occurring after 6 months of therapy. Toxicity was the major reason for switching (61%) and there were no major statistically significant differences in OTSR between the protease inhibitor (OTSR 26.4, 95% CI 18.3-37) and non-nucleoside reverse transcriptase inhibitor (OTSR 22.2, 95% CI 13.6-34.4) based regimes. For individual antiretrovirals, stavudine and zidovudine had significantly higher "switch" scores than all other drugs. There were no differences between the major HAART classes in OTSR. We suggest that newer antiretrovirals will require differentiation in terms of longer-term toxicity, as this is the major reason for switching.
    • "This figure is consistent with previous observational studies among HIV-positive children [17, 24, 40] living in LMIC. Toxicity/intolerance was one of the main reasons reported for substitution (18.3%), mostly related to AZT toxicity (12.4%), as reported in other studies [17, 38, 41]. Due to high prevalence of HIV/TB co-infection (88/769, 11.4%), drug interaction in TB/HIV co-treatment (25.7%) was another major reason to substitute drugs. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Delays detecting treatment failure and switching to second-line combination antiretroviral therapy (cART) are often observed in human immunodeficiency virus (HIV)–infected children of low-middle-income countries (LMIC).
    Full-text · Article · May 2014
    • "The difference may probably be due to limited cART options or the pre-determined population based ART guidelines in these settings, which is likely to influence the clinicians' decision on cART modification. Toxicity was the most common reason for cART modification similar to what has been reported in other studies [8,101112131427]. Stavudine accounted for majority of toxicity related cART modification with risk increasing with time on treatment. "
    [Show abstract] [Hide abstract] ABSTRACT: Limited antiretroviral treatment regimens in resource-limited settings require long-term sustainability of patients on the few available options. We evaluated the incidence and predictors of combined antiretroviral treatment (cART) modifications, in an outpatient cohort of 955 patients who initiated cART between January 2009 and January 2011 in western Kenya. cART modification was defined as either first time single drug substitution or switch. Incidence rates were determined by Poisson regression and risk factor analysis assessed using multivariate Cox regression modeling. Over a median follow-up period of 10.7 months, 178 (18.7%) patients modified regimens (incidence rate (IR); 18.6 per 100 person years [95% CI: 16.2-21.8]). Toxicity was the most common cited reason (66.3%). In adjusted multivariate Cox piecewise regression model, WHO disease stage III/IV (aHR; 1.82, 95%CI: 1.25-2.66), stavudine (d4T) use (aHR; 2.21 95%CI: 1.49-3.30) and increase in age (aHR; 1.02, 95%CI: 1.0-1.04) were associated with increased risk of treatment modification within the first year post-cART. Zidovudine (AZT) and tenofovir (TDF) use had a reduced risk for modification (aHR; 0.60 95%CI: 0.38-0.96 and aHR; 0.51 95%CI: 0.29-0.91 respectively). Beyond one year of treatment, d4T use (aHR; 2.75, 95% CI: 1.25-6.05), baseline CD4 counts ≤350 cells/mm3 (aHR; 2.45, 95%CI: 1.14-5.26), increase in age (aHR; 1.05 95%CI: 1.02-1.07) and high baseline weight >60kg aHR; 2.69 95% CI: 1.58-4.59) were associated with risk of cART modification. Early treatment initiation at higher CD4 counts and avoiding d4T use may reduce treatment modification and subsequently improve sustainability of patients on the available limited options.
    Full-text · Article · Apr 2014
    • "The toxicity rates causing treatment modifications of individual antiretrovirals has not been widely reported. We found a toxicity rate in men for d4T and LPV modifications (32 events per 100 years of follow-up, and 4.7 events per 100 years of follow-up, respectively) similar to cohorts from Chelsea and Westminster in London (30.5 events per 100 years of follow-up and 4.7 events per 100 years of follow-up, respectively) [23]. The toxicity rate of drug modifications for other antiretrovirals (ABC, ddI, NVP, EFV) was somewhat higher in our study populations . "
    [Show abstract] [Hide abstract] ABSTRACT: Background Modifications to combination antiretroviral drug therapy (CART) regimens can occur for a number of reasons, including adverse drug effects. We investigated the frequency of and reasons for antiretroviral drug modifications (ADM) during the first 3 years after initiation of CART, in a closed cohort of CART-naïve adult patients who started treatment in the period 1998–2007 in Croatia. Material/Methods We calculated differential toxicity rates by the Poisson method. In multivariable analysis, we used a discrete-time regression model for repeated events for the outcome of modification due to drug toxicity. Results Of 321 patients who started CART, median age was 40 years, 19% were women, baseline CD4 was <200 cells/mm3 in 71%, and viral load was ≥100 000 copies/mL in 69%. Overall, 220 (68.5%) patients had an ADM; 124 (56%) of these had ≥1 ADM for toxicity reasons. Only 12.7% of individuals starting CART in the period 1998–2002 and 39.4% in the period 2003–2007 remained on the same regimen after 3 years. The following toxicities caused ADM most often: lipoatrophy (22%), gastrointestinal symptoms (20%), and neuropathy (18%). Only 5% of drug changes were due to virologic failure. Female sex (hazard ratio [HR], 2.42 95%; confidence intervals, 1.39–4.24) and older age (HR, 1.42 per every 10 years) were associated with toxicity-related ADM in the first 3 months of a particular CART regimen, but after 3 months of CART they were not. Conclusions Less toxic and better-tolerated HIV treatment options should be available and used more frequently in Croatia.
    Full-text · Article · Jun 2013
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