Multi-state models for the analysis of time-to-treatment modification among HIV patients under highly active antiretroviral therapy in Southwest Ethiopia

Abstract

BackgroundHighly active antiretroviral therapy (HAART) has shown a dramatic change in controlling the burden of HIV/AIDS. However, the new challenge of HAART is to allow long-term sustainability. Toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change. The aim of this study was to evaluate the durability of first line antiretroviral therapy and to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART.MethodsA Hospital based retrospective study was conducted from January 2007 to August 2013 at Jimma University Hospital, Southwest Ethiopia. Data on the prescribed ARV along with start date, switching date, and reason for change was collected. The primary outcome was defined as the time-to-treatment change. We adopted a multi-state survival modeling approach assuming each treatment regimen as state. We estimate the transition probability of patients to move from one regimen to another.ResultA total of 1284 ART naive patients were included in the study. Almost half of the patients (41.2%) changed their treatment during follow up for various reasons; 442 (34.4%) changed once and 86 (6.69%) changed more than once. Toxicity was the most common reason for treatment changes accounting for 48.94% of the changes, followed by comorbidity (New TB) 14.31%. The HAART combinations that were robust to treatment changes were tenofovir (TDF) + lamivudine (3TC)+ efavirenz (EFV), tenofovir + lamivudine (3TC) + nevirapine (NVP) and zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP) with 3.6%, 4.5% and 11% treatment changes, respectively.ConclusionMoving away from drugs with poor safety profiles, such as stavudine(d4T), could reduce modification rates and this would improve regimen tolerability, while preserving future treatment options.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2533-3) contains supplementary material, which is available to authorized users.

Incidence and Predictors of Sever Adverse Drug Reactions Among Patients on Antiretroviral Therapy at Debre Markos Referral Hospital, Northwest Ethiopia

“…Patients with baseline regimen containing stavudine in the combination were at higher risk of developing adverse drug reactions. This is in agreement with previous literature [15,21,24], and it might be because stavudine is known for its typical side effects such as abdominal fat distribution, peripheral neuropathy, lipoatrophy or lipodystrophy, lactic acidosis or severe hepatomegaly with steatosis, and acute pancreatitis [5,25].…”

“…This figure is higher than findings from Bahir Dar city (10%) [13], a tertiary hospital in Addis Ababa (7.7%) [17], seven teaching hospitals in Ethiopia (9.5%) [14], Nigeria (1.4%) [15,16], a tertiary hospital in Ghana (9.4%) [18] and India (2.4%) [19]. The difference might be due to the longer follow up time in the current study which can be explained by the longer the follow-up, the higher the probability of including the ADR [21] and Kenya where it accounted for 66.3% [22]. This can be explained by the proportion of d4T, which causes the majority of regimen changes is lower (29.7%) in this study than the previous studies in Jimma Southwest Ethiopia and Kenya.…”

Incidence and Predictors of Sever Adverse Drug Reactions Among Patients on Antiretroviral Therapy at Debre Markos Referral Hospital, Northwest Ethiopia

“…Patients with baseline regimen containing stavudine in the combination were at higher risk of developing adverse drug reactions. This is in agreement with previous literatures [18,24,27], and it might be because stavudine is known for its frequent side effects on the abdominal fat distribution and other several organs [28].…”

“…Half of the cohort (52.37%) experienced regimen changes, of which 26.37% were due to adverse drug reactions. This finding is lower than findings from Gondar referral Hospital where side effects were the commonest (70.45 %) [23] reasons for regimen change, Jimma Southwest Ethiopia where the change due to ADRs accounted for 48.94% of all changes [24] and Kenya where it accounted for 66.3% [25].…”

Incidence and Predictors of Sever Adverse Drug Reactions Among Patients on Antiretroviral Therapy at Debre Markos Referral Hospital, Northwest Ethiopia

“…The difference might be due to the longer follow up time in the current study which can be explained by the longer the follow up the higher the probability of including the ADR Half of the cohort (52.37%) experienced regimen changes, of which 26.37% were due to adverse drug reactions. This finding is lower than findings from Gondar referral Hospital where side effects were the commonest (70.45 %) [23] reasons for regimen change, Jimma Southwest Ethiopia where the change due to ADRs accounted for 48.94% of all changes [24] and Kenya where it accounted for 66.3% [25].…”