Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral‐naïve patients

Abstract

ObjectivesThe aim of the study was to determine whether the incidence of first-line treatment discontinuations and their causes changed according to the time of starting highly active antiretroviral therapy (HAART) in an Italian cohort. MethodsWe included in the study patients from the Italian COhort Naïve Antiretrovirals (ICoNA) who initiated HAART when naïve to antiretroviral therapy (ART). The endpoints were discontinuation within the first year of 1 drug in the first HAART regimen for any reason, intolerance/toxicity, poor adherence, immunovirological/clinical failure and simplification. We investigated whether the time of starting HAART (stratified as 'early ', 1997-1999; 'intermediate', 2000-2002; 'recent', 2003-2007) was associated with the probability of reaching the endpoints by a survival analysis. ResultsOverall, the 1-year probability of discontinuation of 1 drug in the first regimen was 36.1%. The main causes of discontinuation were intolerance/toxicity (696 of 1189 patients; 58.5%) and poor adherence (285 of 1189 patients; 24%). The hazards for all-reason change were comparable according to calendar period [2000-2002, adjusted relative hazard (ARH) 0.82, 95% confidence interval (CI) 0. 69-0.98;2003, ARH 0.94, 95% CI 0.76-1.16, vs. 1997; global P-value 5 0.08]. Patients who started HAART during the 'recent' period were less likely to change their initial regimen because of intolerance/toxicity (ARH 0.67, 95% CI 0.51-0.89 vs. 'early' period). Patients who started in the 'intermediate' and 'recent' periods had a higher risk of discontinuation because of simplification (ARH 15.26, and ARH 37.97, vs. 'early' period, respectively). ConclusionsIt seems important to evaluate reason-specific trends in the incidence of discontinuation in order to better understand the determinants of changes over time. The incidence of discontinuation because of intolerance/toxicity has declined over time while simplification strategies have become more frequent in recent years. Intolerance/toxicity remains the major cause of drug discontinuation.

Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL

“…This result is in line with previous observational data on triple therapy in the observational cohort studies [17,18].…”

Efficacy of 1998 Vs 2006 First-Line Antiretroviral Regimens for HIV Infection: An Ordinary Clinics Retrospective Investigation

“…In our study, however, the incidence of toxic events in the sample years was surprisingly similar, differing from those of previous studies [35,39] and in line with another recent report [19]. This may be partly related to the epidemiological trends and clinical differences evidenced in the 2 sample populations, as the higher proportion of younger and less advanced patients in 1998 may have possibly counterbalanced the higher toxicity of first generation drugs used in that year [40,41].…”

Antiretroviral changes during the first year of therapy

“…22 In one study, 21 virological failure combined with viral resistance occurred in 24.1% of patients with interruption and resumption of treatment using stavudine (d4T) + 3TC + NVP, d4T + 3TC + EFZ and AZT + 3TC + NVP regimens. Other studies showed that d4T regimens had virological failure in 16.9%, motivated by predictors such as treatment interruptions, use of NVP, initial LTCD 4 < 25 cells/dL, initial VL ≥ 400 copies/mL, and stage of AIDS, 14,16,17,19,20 while only 7.7 and 2.65% obtained treatment failure with the same regimens in other studies. 18,25 These differences may be justified by factors such as ARV classes (NRTI, NNRTI and PI), adherence, toxicity, adverse reactions, incorrect drug combinations in coinfections, and pharmacogenetics of patients.…”

“…These data are in agreement with results obtained by several authors, which show similar correlations between the antiretroviral drugs and their main clinical and laboratory alterations. 14,15,17,[25][26][27] Other studies also reveal that changes in HAART after six months may also occur after confirmation of immuno-virological failure and low adherence. 16,17,[19][20][21] In our population, therapeutic failure, although not the most prevalent cause for HAART replacement, was the reason for switching drugs in 12.6% of the cases that used initial TDF + 3TC + EFZ and AZT + 3TC + EFZ regimens.…”

“…13 Studies in Spain, Italy, the United States and India also point to an increasing prevalence of HIV infection among men. [14][15][16][17][18] AIDS was diagnosed in 64.4% of the patients, which can be explained by problems of adherence to HAART and/or late treatment start, according with LTCD 4 count and VL profile, which makes immune reconstitution and viral suppression more difficult with onset of resistance, directly reflecting the appearance of AIDS coinfections and symptoms in 15 to 61% of patients. 7,[19][20][21][22] In the 87 patients studied, LTCD 4 increase was significant between the fifth and eighth month of treatment.…”