Determinants of anti-retroviral regimen changes among HIV/AIDS patients of east and west Wollega zone health institutions, Oromia region, west Ethiopia: a cross-sectional study

Human immunodeficiency virus (HIV) annihilates and compromises the function of immune cells. Immunity of infected individuals gradually depletes and susceptibility to a wide range of infections and diseases would be boosted. Acquired immunodeficiency syndrome (AIDS) is the most advanced stage of HIV infection, which can take from 2 to 15 years to develop depending on the individual and it can be explained by the progression of opportunistic infections, or other intense clinical manifestations and certain cancers [1, 2].

HIV is one of the main causes of morbidity and mortality; because of this it continues to be a major global public health concern. It has believed to kill more than 34 million lives so far. Sub Saharan Africa constitutes about 70% of people living with HIV among the thirty seven million on the globe. This region, accounted for more than two third of the global new HIV infections in 2014 with only 12% of the global population. Globally people receiving ART were about fifteen million (40%) among those living with HIV of which about fourteen million were in low- and middle –income countries and nearly one million were children [2].

Ethiopia is among the countries most affected by HIV/AIDS with prevalence of 1.9% for women and 1.0% for men in 2011 [3] and it is also in a low generalized HIV epidemic with significant heterogeneity among regions and population groups [4]. The existence of HIV infection in Ethiopia was recognized in the early 1980s with the first two AIDS cases reported in 1986. The predominant strain is HIV-1 subtype C, predominantly spread through unprotected heterosexual intercourse [5]. Since 2000 the epidemic has declined [6] and recent figures show that HIV infection has significantly decreased over the years in the country [4].

Highly active antiretroviral therapy (HAART) has fundamentally changed the treatment of HIV and changed this infection from a disease of high mortality to chronic and medically managed disease which is a radical change in controlling the hardship of HIV/AIDS. However drug resistance and side effects were the great concern in these advancements [7]. Revolution in the care of patients with HIV/AIDS occurred due to the innovation of potent HAART in around 2000. The qualities of life of people living with HIV/AIDS (PLWHA) have improved and these treatments have dramatically reduced rates of mortality and morbidity among these patients. This result was also confirmed by World health organization (WHO) progress report. ARV drugs produce these effects by restoration of number and quality of cluster of difference (CD4) cells and suppressing viral replication [8].

The goal of ART is to attain maximal and durable suppression of the viral replication. Viral suppression enables recovery of the immune response and thereby reduces risk of opportunistic infections (OIs) and death [1].

The decision to initiate ART for adults and adolescents depend on: WHO stage 3 and 4 disease irrespective of CD4 cell count, CD4 count ≤500cells/mm³ irrespective of WHO clinical stage and active tuberculosis (TB) co-infection with HIV irrespective of CD4 cell count according to standard treatment guideline of Ethiopia [6].

Triple combination therapy has been in use for more than two decades globally. Currently, the preferred first regimen triple therapy in Ethiopia consists of, two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and one Protease Inhibitor (PI) or a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) or a triple therapy of three NRTIs. Based on the guideline, common ART regimens in the country are; Tenofovir (TDF)/ Emtricitabine (FTC)/ Efavirenz (EFV) or Nevirapine (NVP); alternatives are TDF/ Lamivudine (3TC) /EFV or NVP, Zidovudine (ZDV)/3TC/EFV or NVP. Other options are Abacavir (ABC)/3TC/NVP, ABC/3TC/EFV and ABC/3TC/ZDV. The second line regimen consists of ZDV ±3TC + Lopinavir/ritonavir (LPV/r) (or Atazanavir/ritonavir (ATV/r)), ZDV + ABC + LPV/r (or ATV/r), TDF/3TC ± ZDV + LPV/r (or ATV/r), ABC/ Didanosine (ddI) /LPV/r (or ATV/r), EFV or NVP / LPV/r (or ATV/r) [1, 9].

Changes of multiple medications in HAART regimens were commonly required simultaneously. These changes may be due to co morbidity with other chronic diseases, a desire for pregnancy, poor adherence, stock out of drugs, treatment failure, long term toxicity or acute toxicity. The approaches to change ART regimens depend largely on amount of previous ART experience, available treatment options and reason for change. For example effective treatment can be accomplished by substituting another agent for the drug which has unpleasant effect in the regimen when it develops to certain drugs in the regimen [7, 10].

The issues of drug toxicities and complexity of current HAART regimens has remained of great concern despite ARTs being of much help to the health of HIV/AIDS patients. Suboptimal therapy, discontinuation, and treatment failure can be resulted from treatment toxicities and adherence problems [11]. The consequence of these may complicate the management and lead to toxicity, loss to follow-up, compromise the effectiveness of HAART regimens, drug interactions and drug resistance [12].

Knowledge of the determinants of ART change may help to minimize the risk factors. These benefits in decreasing the rate of regimen change, treatment failure, drug resistance, and improve the quality of life of the patient. Antiretroviral treatment change should be done when necessary to spare the future treatment options. The approach to patients who need to switch will differ depending on several issues, including ART experience and available options. Regimen substitution requires adjustment in learning the new medication about the treatment dosing, time of intake and deal with many individual based inconveniences, which might be challenging and reason for non-adherence [10, 13].

Data on modification of HAART and factors associated with ARV drug regimen change are limited among HIV/AIDS patients in Ethiopia. Most of the surveys used were on small sample of patients who were on ART for less than three years. As a result it is important to understand common reasons of ARV drug switch in patients on long period exposure to ART.

Therefore, this study attempts to investigate the major determinants of HAART regimen change among HIV/AIDS patients in east and west Wollega zone health institutions by using cross-sectional study.

The present retrospective cross sectional study of HIV/AIDS patients who changed their HAART regimen in east and west Wollega zone health institutions described the pattern of ART regimen and the common reasons for ARV drug switch. Such studies would be helpful in understanding the complexity of ART use of patients in health institutions which might have different co morbidities.

Majority of the study population 145 (59.67%) had been on ART for > 10 years. This finding indicated longer duration as compared to other studies as all patients stayed on ART for less than 3 years in Bedelle [15] and in Addis Ababa about 98% of patients stayed on ART for less than one and half years and in Dessie only 6% patients stayed on ART for more than 2 years [10, 16].

The main reason for initial ARV drug switch in the present study was toxicity which was known as peripheral neuropathy and it accounted for more than 60% of HAART regimen change. This finding was in agreement with the study conducted in some parts of Ethiopia [10]. The other reasons for HAART regimen change were hepatotoxicity 22(9.1%), anemia 16(6.6%) and rash15 (5.3%). The combined sum of hepatotoxicity, anemia and peripheral neuropathy was more than 80%, which was much higher than the studies done in United Kingdom (35%) [17] and India (27%) [18]. However, it was almost similar to the studies conducted in other parts of Ethiopia as it was 75.8% in Mekelle [19] and 66% in Dessie [16]. But there was a significant heterogeneity on the type of toxicities in these studies.

Change of the entire regimen from first-line to second-line is required in case of treatment failure. In order to increase likelihood of treatment success and minimize the risk of cross-resistance the new second-line regimen should involve drugs that keep activity against the patient’s virus strain and should preferably include at least three new drugs, one or more from a new class [12]. The preferred strategy for second-line ART for adults is using a boosted PI and two NRTI combinations when NNRTI-containing regimens were used in first-line ART [8]. Patients from low-income countries were less likely to change two or more drugs and to change to a protease-inhibitor-containing regimen when compared with patients from high-income countries [20].

The study also found that there was high prevalence of TB as almost three out of five patients (57%) had received isoniazid & cotrimoxazole prophylaxis and more than half (52%) of the patients had been treated for TB [16, 19]. NVP has high interaction with Rifampicin which is strong liver enzyme (CYP 3A4) inducer where by therapeutic level of NVP is decreased up to 40% which necessitates switch to EFV. Additive hepatotoxicity effects also exists when NVP and Rifampicin were used together according to findings of some studies which is another requirement to switch from NVP to EFV as the latter has lesser adverse drug reaction with Rifampicin [21].

The number of patients who changed ARV drug in our resource constrained setting present a challenge to the restricted treatment choices that we currently own. The main reasons for ART switch were toxicity among which Peripheral neuropathy and hepatotocity were the leading toxicity for ART switch. Less toxic and better-tolerated HIV treatment options should be available and used more frequently in east and west Wollega zone health institutions. Patient should be evaluated regularly after a treatment change to assess for potential concerns with the new regimen, medication tolerance and to assess the effectiveness. Information is needed on patterns of resistance across the population to recommend future therapy options. Therefore national and health institution based surveillance of antiretroviral drug resistance should be conducted. It helps to know the resistance pattern and select the locally effective treatments. National level study on reasons for regimen change should be done to help drug suppliers and policy makers to improve and solve the problem. The reasons of ARV drug switch observed in this cross sectional study should be investigated further in longitudinal multicenter studies of ART utilization.