Reasons for modification and discontinuation of antiretrovirals: Results from a single treatment centre

Department of Primary Care and Populations Sciences, Royal Free Centre for HIV Medicine, Royal Free and University College Medical School, London, UK.
AIDS (Impact Factor: 5.55). 02/2001; 15(2):185-94. DOI: 10.1097/00002030-200101260-00007
Source: PubMed

ABSTRACT To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic.
A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC).
The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART.
There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.

Download full-text


Available from: Anne M Johnson, Jan 14, 2015
12 Reads
  • Source
    • "This difference is likely due to close treatment monitoring or potential selection bias of persons enrolled in clinical trials and programs as compared to those in routine clinical settings. The rates are however still lower than those observed in developed nations where cART modifications are as high as >50% [9], [25], [26]. 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. "
    [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.
    PLoS ONE 04/2014; 9(4):e93106. DOI:10.1371/journal.pone.0093106 · 3.23 Impact Factor
  • Source
    • "The findings of this review are supported by previous studies reporting on the impact of HIV treatment-related AEs. In the Italian Cohort of Antiretroviral-Naïve Patients, 21.1% of participants discontinued combination ART due to treatment toxicity over a median follow-up period of 45 weeks, whereas only 5.1% of participants in the same population discontinued therapy due to treatment failure (Mocroft et al., 2001; Monforte et al., 2000). Moreover, a study conducted by Stone et al. (2001) in the HIV Epidemiology Research cohort, indicated that patients who reported having two or more adverse reactions to ART were more likely to discontinue treatment than patients who did not experience these reactions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Poor adherence to antiretroviral therapies (ARTs) in human immunodeficiency virus (HIV)-infected patients increases the risk of incomplete viral suppression, development of viral resistance, progression to acquired immune deficiency syndrome and death. This study assesses the impact of specific treatment-related adverse events (AEs) on adherence to ART in the adult HIV patient population. A systematic review of studies involving adult HIV-infected patients aged ≥ 16 years that reported an odds ratio (OR) for factors affecting adherence to ART was conducted through a search of the EMBASE® and Medline® databases. Database searches were complemented with a search of titles in the bibliographies of review papers. Studies conducted in populations limited to a particular demographic characteristic or behavioural risk were excluded. To qualify for inclusion into a meta-analysis, treatment-related AEs had to be defined similarly across studies. Also, multiple ORs from the same study were included where study sub-groups were distinct. Random effects models were used to pool ORs. In total, 19 studies and 18 ART-related AEs were included in meta-analyses. Adherence to ART was significantly lower in patients with non-specific AEs than in patients who did not experience AEs [OR = 0.623; 95% confidence interval (CI): 0.465-0.834]. Patients with specific AEs such as fatigue (OR = 0.631; 95% CI: 0.433-0.918), confusion (OR = 0.349; 95% CI: 0.184-0.661), taste disturbances (OR = 0.485; 95% CI: 0.303-0.775) and nausea (OR = 0.574; 95% CI: 0.427-0.772) were significantly less likely to adhere to ART compared to patients without these AEs. Knowledge of specific treatment-related AEs may allow for targeted management of these events and a careful consideration of well-tolerated treatment regimens to improve ART adherence and clinical outcomes.
    AIDS Care 08/2012; 25(4). DOI:10.1080/09540121.2012.712667 · 1.60 Impact Factor
  • Source
    • "Other biomedical and behavioral research has focused on the way health personnel relate with a patient, the type of pharmacologic regimen, and the existence or not of family and social support (Burke et al., 2003; Chesney et al., 2000; Chesney, Morin, & Sherr, 2000; Correa, Salazar & Arrivillaga, 2007; Jia et al., 2004). Some studies have found associations between adherence and sociodemographic factors such as age, gender, and education (Carballo et al., 2004; Glass et al., 2006; Godin, Co Ï t e, Naccache, Lambert, & Trottier, 2005; Gordillo, Del Amo, Soriano, & Gonzalez, 1999; Ickovics & Meade, 2002; Mocroft et al., 2001; Spire et al., 2002; Sternhell & Corr, 2002). Because results on the association between adherence and socioeconomic status (SES) have not been consistent (Falagas, Zarkadoulia, Pliatsika, & Panos, 2008), further research is needed to understand the role SES and other social determinants may play in adherence. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Studies on HIV/AIDS treatment adherence have been carried out in a limited number of geographic settings, but few studies have explored it in people of higher socioeconomic status in Latin America. This qualitative study explored and compared determinants of adherence behaviors among 52 HIV-positive Colombian women in medium and high socioeconomic positions (SPs). Findings indicated that the two SP groups reported high adherence behaviors related to taking medication, following a diet, and executing lifestyle changes in line with healthcare providers' recommendations. Nevertheless, differences were observed between the two groups. While women with a medium SP disclosed their diagnosis, were empowered, and had acceptable access to economic resources that resulted in favorable adherence, their better off counterparts tended to hide their status and made a conscious effort to keep their adherence behaviors in secret due to HIV-related stigma. More studies on adherence of people living with HIV/AIDS from high SPs should be conducted to better understand how psychosocial support can be provided and to advance the knowledge of how and why adherence practices in these groups are undertaken.
    AIDS Care 01/2012; 24(7):929-35. DOI:10.1080/09540121.2011.647678 · 1.60 Impact Factor
Show more