THE REASONS FOR ANTIRETROVIRAL REGIMEN CHANGE AMONG PEOPLE LIVING WITH HIV/AIDS IN ASELLA REFERAL HOSPITAL.
Abstract
Background and aim: Highly active antiretroviral therapy (HAART) is the cornerstone of management of patients with HIV infection. On the other hand, a switch in the antiretroviral regimen is often necessary because of various reasons. Therefore, the objective of the present study was to determine the reasons for initial antiretroviral regimen change among adult HIV/ADIS patients.
Methods: A retrospective cross-sectional study was conducted on patient information records of those visited the ART clinic since February, 2013 to January, 2015 in Asella Referral Hospital. Results: From 1468 patients’ medical information reviewed, 221 of them changed their initial HAART regimens. Among these patients, 38% of them changed their initial medications because of drug toxicity which was mainly triggered by AZT/3TC/NVP. The major cause for changing AZT/3TC/NVP treatment regimen associated with drug toxicity was anemia (17.85%). Other reasons stated for medication shift were co-morbidity, treatment failure, poor adherence and pregnancy.
Conclusion: Since most of regimen modifications were due to drug toxicity, these regimen shifts require careful follow up; frequent laboratory result monitoring and selection of appropriate antiretroviral regimens.
Key words: Antiretroviral therapy, HIV/ADIS, Regimen change, Asella
Introduction
Globally, an estimated about 35.3 million people were living with HIV at the end of 2012 [1]. Sub-Saharan Africa continues to bear a disproportionate share of the global HIV burden. Accordingly, in mid-2010, about 68% of all people living with HIV resided in sub-Saharan Africa, a region with only 12% of the global population [2, 3]. Similarly, the HIV/AIDS epidemic in Ethiopia continues to pose a threat to the lives of its people with an estimated of 793,700 people living with HIV; resulting, a prevalence rate of 1.5% [4].
As highly active antiretroviral therapy (HAART) is the cornerstone of management of patients with HIV infection, initiation followed by widespread use of antiretroviral therapy has brought a marked decline in the incidence of most AIDS defining conditions and mortality [5,6]. However, these advancements were not without a cost in terms of drug resistance and adverse effects [7].
Once antiretroviral therapy (ART) is initiated, patients generally remain on medications indefinitely. However, a switch in the antiretroviral (ARV) regimen is often necessary because of toxicities, concomitant clinical conditions, and development of virologic failure [8]. Moreover, different literatures reported that toxicity or adverse drug reaction (ADR), co-morbidity, treatment failure and drug-drug interactions are the main reasons for ART regimen change or modification [9-13].
There is no study yet conducted in the study area in particular and few data available in Ethiopia in general on reasons causing for regimen change among HIV/AIDS patients who were already on ART. Hence, this data can potentially help to draw a long term strategic plan for ART drug management. Therefore, the objective of this study was to determine the reasons for HAART regimen change among HIV/AIDS patients in Asella Referral Hospital.
Methods
The study was conducted in Asella Referral Hospital, which is located at 175 km away from the capital city, Addis Ababa from February to January, 2015. The hospital provides different services: outpatient and inpatient services; mother and child health care, and ART services.
Hospital based retrospective cross sectional study was conducted by reviewing patient record cards. Patient information cards of all HIV/AIDS positive patients who were on HAART in the ART Clinic from February 2013 to January 2015 were the source of the population, while HIV/AIDS patients who switched initial antiretroviral therapy regimen were included in the study. Accordingly, within two years a total of 1468 patients visited the clinic; however, only 221 of them switched their initial regimen. Hence, the study included all of the 221 patient cards of those shifted their initial regimen.
A data collection instrument was developed by reviewing different relevant literatures. The tool was evaluated for its validity, reliability and consistency. Then, it was used to collect data from patient record cards. The collected data was then checked, categorized and analyzed using MS excel and SPSS version 19. Finally, the results were presented using tables and figures.
Ethical clearance was obtained from an ethical clearance committee of Health Sciences College of Jimma University. Then, the letter was given to the administrator of Assela Referral Hospital to get permits for data.
Results
From 1468 patients’ medical information reviewed, 221 of them changed their initial HAART regimen. More than half of the patients were females (57.64%). And most of the patients (20.81%) were in the age group of 26-30. Regarding CD4 count, about half of patients (52.40%) had an initial CD4 count greater than 200 whereas only 10% of the patients had CD4 counts less than 50% (Figure1).
Among the patients who modified their initial regimen, 38% of them changed their initial medications because of drug toxicity which were primarily due to AZT/3TC/NVP (40.5%). Other regimen switches were owing to toxicity triggered by TDF/3TC/EFV (15.5%), D4T/3TC/NVP (13.1%), D4T/3TC/EFV (11.9%), AZT/3TC/EFV (10.7%) and TDF/3TC/NVP (8.3%) regimens. Pregnancy was the other cause of the regime change in 21 patients, of whom the majority of them (33.3%) shifted AZT/3TC/NVP regimen. On the other hand, from patients who modified their initial regimen as a result of co-morbid conditions and treatment failure, six and twelve of them were initially on AZT/3TC/NVP and D4T/3TC/NPV, respectively. Tuberculosis was the only reported co-morbid diseases triggering a shift of initial regimen among 11 patients (Table 1).
One of the major reasons for regimen shift related to drug toxicity was anemia, which were due to AZT/3TC/NVP and AZT/3TC/EFV regimen among 15 (17.85%) and 4 (4.76%) patients, respectively. The other main reasons determined for initial regimen switch were nausea due to D4T/3TC/EFV (8.33%) and AZT/3TC/NVP (8.33%); rash as a result of AZT/3TC/NVP (10.71%) D4T/3TC/NVP (4.76%); peripheral neuropathy because of D4T/3TC/NVP (5.95%) and TDF/3TC/EFV (5.95%) (Table 2).
The majority of patients (32.1%) shifted the regimen in the first three months because of drug toxicity and only 7.1% of patients continued their initial regimen for more than 104 weeks. Similarly, in case of patients with co-morbid conditions, poor adherence and pregnancy, most of them switched their initial regimen in the first three months (the first 12 weeks) which were accounting for 36.4%, 33.3% and 42.9%, respectively. Moreover, 37.0% of patients changed their first regimen in 26-52 weeks as a result of treatment failure (Table 3). Most of these patients shifted their medication because of immunological failure (57.4%) (Figure 2).
Discussion
There are many reasons that lead to ineffectiveness, change of HAART combination and discontinuation of HAART regimen. The rational for treatment switch and discontinuation of the medications might belong to toxicity, treatment failure (virological, immunological and clinical failure), poor adherence, a desire for pregnancy, and co-morbidity [7]. In the present study majority of patients who changed their initial medication were because of drug related toxicity. This finding is consistent with the study done in Southern Ethiopia [8] and in Ceará, Brazil [9]. The most frequently reported toxicity related causes for modification of initial regimen were nausea, rash, anemia and peripheral neuropathy. Similar finding was reported in the retrospective cohort study conducted in New Orleans, LA., USA [11].
Both anemia and rash were reported as the main cause of medication related toxicity triggering initial treatment regimen shift owing to AZT/3TC/NVP which is consistent with other research finding reported by Woldemedhin and Wabe [14]. But, it is dissimilar with other study done in Nekemete Referral Hospital [15]. Regimens such as D4T/3TC/EFV and AZT/3TC/NVP; D4T/3TC/NVP and D4T/3TC/EFV were the major causes stated for peripheral neuropathy and nausea, respectively.
Co-morbidities in patients with advanced diseases and concurrent treatments for opportunistic infections could affect antiretroviral tolerance and thereby increase the risk of toxicities [11]. This could be as result of pill burden which is to be taken simultaneously to treat both ADIS and opportunistic infection. However, tuberculosis was the only co- morbid diseases reported in this study which triggered the regimen modification. This is consistent with the study conducted in the UK [16] and Coited’lvoire [17].
Treatment failure was also reported as the main reason for the regime shift in 54 (23.6%) of the patients in the current study. Similarly, in the study conducted in Coited’lvoire [17] and Uganda [18], it was reported that treatment failure was one of the major reasons for discontinuation and modification of initial regimen.
Among patients who switched their regimen due to medication toxicity, the majority of them shifted the regimen in the first three months and only few of the patients continued their initial regimen for more than 104 weeks before first switch. This finding is incomparable with the study conducted in Durame Hospital where the majority of them change their medication after 104 weeks [19].
Conclusion
The main reason for regimen modifications was toxicity. Peripheral neuropathy, nausea, anemia, and rash were the main manifestation of drug toxicities triggering modification of HAART. Most of drug toxicities and regimen modification were incurred from NVP-based regimen mainly AZT/3TC/NVP. Hence, careful follow up; frequent laboratory result monitoring, and selection of appropriate antiretroviral regimen must be carried out to prevent drug toxicity and enhance patient adherence.