Acknowledgment

Primarily, I want to specially thank the Almighty GOD for giving me the inspiration to start and
patience until I will finalize this research proposal work. Secondly, I want to extend my sincere
appreciation to my advisor, Mr. Getu Bayisa, for his valuable advice, constant support,
commitment, dedication, encouragement and precious guidance, creative suggestions and critical
comments, and for being everlasting enthusiastic from the beginning to the end of the research
proposal.
Moreover, I sincerely thank to Wollega University, Faculty of Health Sciences, and Department
of Pharmacy for giving me this opportunity
Good girl fuck her own pussy with

banana

Table of Contents
Abstract……………………………………………………………………………………………………I
Acknowledgements………………………………………………………………………………………II
Abbreviations……………………………………………………………………………………………III

List of Tables …………………………………………………………………………………………….VI

1. Introduction.................................................................................................................................................................9
1.1. Background..............................................................................................................................................................9
1.2. Statement of the problem.......................................................................................................................................12
1.3. Literature Review...................................................................................................................................................13
1.4. Significance of the study........................................................................................................................................15
2. Objective...................................................................................................................................................................16
2.1. General objective...................................................................................................................................................16
2.2. Specific objectives.................................................................................................................................................16
3. Methodology.............................................................................................................................................................17
3.1. Study area and period.............................................................................................................................................17
3.3. Inclusion and Exclusion Criteria............................................................................................................................18
3.4. Sample Size Determination and Sampling Technique...........................................................................................18
3.6. Study Variables......................................................................................................................................................19
3.6.1. Independent Variables................................................................................................................................19
3.6.2. Dependent Variables..................................................................................................................................19
3.7. Data Procedure and Management..........................................................................................................................19
3.7.1. Data collection procedure...................................................................................................................................19
3.7.2. Data Collectors Recruitment and Training.........................................................................................................20
3.8. Data Analysis Procedures......................................................................................................................................20
3.9. Ethical considerations............................................................................................................................................20
3.10. Operational Definitions...................................................................................................................................21
4. Work plan and budget breakdown............................................................................................................................22
4.1 Work plan................................................................................................................................................................22
Table 1work plan..........................................................................................................................................................22
4.2 Budget breakdown..................................................................................................................................................23
Table 2 .Budget Break Down........................................................................................................................................23
References:....................................................................................................................................................................25
List of Tables
Table 1. Work Plan

Table 2 .Budget Break Down…………………………………………………………………….

Abbreviations and Acronomy
ABC Abacavir

ARV Antiretroviral

ART Antiretro Viral Therapy

D4T Zidovudine

NVP Nevirapine

EFV Efavirenz

ETC Emitricibine

VL Virological Load

HAART Highly Active Antiretroviral Therapy

PLWHA People living With HIV/AIDS

PI Protease Inhibitors

3TC Lamivudine
Abstract

Background: HIV continues to be a major global public health issue, having claimed more than
34 million lives so far. Globally there were approximately 37 million people living with HIV and
about 15 million (40%) were receiving antiretroviral treatment (ART) at the end of 2014. ART
has revolutionized the treatment of HIV and transformed this infection from a fatal to a
medically managed disease.
Objective: The objective of this study will be to determine factors leading to antiretroviral
regimen change among HIV/AIDS Positive Patients in Nekemte Referral Hospital, East Wollega
Zone, West Ethiopia

Methodology: The study will be a hospital based retrospective cross-sectional study conducted
from April.28 to May 30/ 2017 in the ART Clinic of Nekemte Referral Hospital , using a pre-tested data
collecting form and chart review. Among patients who experienced antiretroviral drug regimen
change, 118 will be included in the study using systematic random sampling.

Key words: HIV, ARV Drug Regimen Change, Factors, Reason for Change
1. Introduction

1.1. Background

Human immune deficiency virus/acquired immune deficiency syndrome (HIV/AIDS) has first
appearance in 1981 and remains a major global public health challenge; with dramatic
consequences for entire communities [1]. HIV has killed more than 25 million people worldwide
since the first diagnosis in 1981. In the 1980’s and 1990’s HIV/AIDS was the major cause of
death among adults [2]. According to the joint 2011 HIV/AIDS report of World Health
Organization (WHO), Joint United Nations programme on HIV/AIDS (UNAIDS), and United
Nations Children’s Fund (UNICEF), an estimated 34 million people were living with HIV/AIDS
globally with 2.7 million new HIV infections in 2010. Of these, 68% were residing in sub-
Saharan Africa [3]. Ethiopia is one of the seriously affected countries in sub-Saharan Africa with
a large number of people (approximately 800,000) that are living with HIV/AIDS and 44,751
AIDS-related deaths [4].
Until 1995, treatment for HIV infection consisted mainly of single-drug and dual-drug therapy
regimens that provided limited success. With the introduction of protease inhibitors (PIs), HIV
viral loads and AIDS related deaths has declined dramatically. At present, combination therapy
involving three classes of antiretroviral drugs—nucleoside reverse transcriptase inhibitors
(NRTIs), non-NRTIs (NNRTIs), and PIs—formed the basis of potent anti-HIV regimens known
as highly active antiretroviral therapy (HAART) [5]. When taken diligently, these regimens have
improved patients' prognosis by delaying the emergence of resistant strains of virus, thereby
slowing the progression of HIV infection to AIDS. Observational and retrospective cohort
studies from many countries have confirmed striking improvements in mortality with
combination Anti-Retroviral Therapy (ART); compared to earlier one- or two-drug regimens
[6].This combination therapy caused gradual evolution of HIV/AIDS from a fatal disease to a
chronic condition. A total of 2.5 million deaths have been averted in low- and middle-income
countries since 1995 due to antiretroviral therapy being introduced. Actually in 2010 alone,
700,000 AIDS related deaths were averted due to the rapid scale-up of access to treatment [7].
According to the Standard Treatment Guideline of Ethiopia, 2014; the criteria for initiating ART
for adults and adolescents were: WHO stage 3 and 4 disease irrespective of CD4 cell count, CD4
count ≤500cells/mm3 irrespective of WHO clinical stage and Active TB co-infection with HIV
irrespective of CD4 cell count. Triple combination therapy has been in use for more than two
decades globally. Currently, the preferred first regimen triple therapy in Ethiopia is
TDF/FTC/EFV or NVP Alternatives are TDF/3TC/EFV or NVP, ZDV/3TC/EFV or NVP. Other
options are ABC/3TC/NVP, ABC/3TC/EFV and ABC/3TC/ZDV. The second line regimen
consists of ZDV ±3TC +LPV/r (or ATV/r), ZDV+ABC+LPV/r (or ATV/r), TDF/3TC± ZDV +
LPV/r (or ATV/r), ABC/ddI /LPV/r (or ATV/r), EFV or NVP / LPV/r (or ATV/r) [8].

HAART regimens commonly require changes, which often involve switches of multiple
medications simultaneously. A treatment switch may be either because of the risk of acute
toxicity, long-term toxicity, treatment failure, poor adherence, a desire for pregnancy, co-
morbidity with other chronic diseases or stock out of drugs The approach to switch ART depends
on the reason for change, the amount of previous ART experience, and the available treatment
options. For example, when patients develop an adverse effect to a drug, effective treatment may
be easily accomplished by substituting another agent for the offending drug in the regimen.
Patients who have experienced toxicities, treatment failure, and drug resistance during past
regimens may require a new treatment regimen [9, 10].

Patients should be evaluated after a treatment switch to assess for potential concerns with the
new regimen, medication tolerance and conduct targeted laboratory testing. For example, if lipid
abnormalities were present and/or were a reason for the ARV change or are a concern with the
new regimen, fasting cholesterol subsets and triglycerides should be assessed within 3 months
after the change in therapy. If any specific complaints, laboratory abnormalities, or viral rebound
are absent at 3-month visit, the patient may resume on a regularly scheduled basis [11].

The WHO definition treatment failures for the decision to switch ART regimens can be clinical,
immunological or virological. Clinical failure is occurrence of new or recurrent clinical event
indicating severe immunodeficiency after 6 months of effective treatment. Immunological failure
is when CD4 count falls to the baseline (or below) or Persistent CD4 levels below 100 ells/mm3.
Finally, a virological failure is when plasma viral load is above 1000 copies/ml based on two
consecutive viral load measurements after 3 months, with adherence support [12].

There are many factors that may lead to treatment failure such as: inadequate adherence; drug
side effects and toxicity leading to poor adherence, drug-drug interaction between the ARVs and
other concomitantly administered drugs resulting in sub-therapeutic ARV concentrations, and
suboptimal potency of the ARV regimen that will lead to short survival of patient on ART.
Virologic failure, immunologic failure and clinical failure have distinct time course and may
occur independently or simultaneously. In general, virologic failure occurs first followed by
immunologic failure and finally clinical failure. These events may be separated by months to
years. The delay between virological and immunological failure carries the risk of exposing HIV
to failing regimen. This can lead to development of further cross resistance, which compromises
the efficacy of the second line regimen. Thus, viral load monitoring offers the advantages of
detecting treatment failure early and preventing accumulation of further resistance mutations.
Hence, plasma viral load determination is recommended every six months to identify virological
failure early [13, 14].
1.2. Statement of the problem
Despite ARTs being of much help to the health of HIV/AIDS patients, the issues of drug induced
toxicities & complexity of current HAART regimens has remained of great concern. Treatment
toxicities and adherence problems may lead to suboptimal therapy, discontinuation, and
treatment failure [15]. These influences may compromise the effectiveness of HAART
programmes, complicating the management and lead to toxicity, drug interactions, loss to
follow-up and drug resistance amongst diverse populations such as Ethiopia [16].

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.
Knowing the reasons for ART change may help to minimize the risk factors. These lead to
decrease the rate of regimen change, treatment failure, drug resistance, and improve the quality
of life the patient [17, 10].

Data on modification of ART and factors associated with ARV drug regimen change are limited
among HIV patients in Ethiopia. Most studies in Ethiopia are on small sample of patients who
were on ART for less than three years. Even though the Nekemte Referal hospital ART clinic
has begun provision of medications since March 2005, as to knowledge of the principal
investigator there is no research done regarding pattern of ARV drug regimen change and the
associated reasons for the switch. Thus this study will be conducted with an aim to assess the
reasons contributing for the change of ART regimen among patients with HIV/AIDS in Nekemte
Referal Hospital. As this study included patient data for the past ten years it enables to know the
common reasons of ARV drug switch in patients on long period exposure to ART. In addition,
this study would identify the extent of second and third time ARV drug switch and the
determinant factors associated with these multiple switches. Furthermore, this study elucidates
the patterns of ARV drug switches in Nekemte Referal hospital.
1.3. Literature Review
Antiretroviral drug modifications (ADM) due to toxicity have been reported to be associated
with many factors: demographic characteristics such as female sex, age, ethnicity, genetics, HIV
disease status, type of ART, and co-morbidities. It has also been reported that toxicity-related
ADM are most frequent within the first 3 months of ART. Majority of the studies, however, have
focused on the first event of ADM .In a 2010 study of 1318 treatment-naive patients, switches or
discontinuations because of drug toxicity occurred at a rate of 22 per 100 person-years. The most
frequent adverse effects were gastrointestinal intolerance (29 %), hypersensitivity (18 %), CNS
side effects (17 %), and hepatic events (12 %) [18].

A study analyzed 5026 adult HIV infected patients, who were being on ART between 1996 and
2007 in 7 Sites throughout the Caribbean and Latin America. The primary reason for change
among HAART initiators were: adverse events (14%), death (5.7%) and failure (1.3%) with
specific toxicities varying among sites. After change, most patients remained in first line
regimens [19].

An observational cohort study in the Asia and Pacific region indicated that among 2446 patients
who initiated ART, 447 were documented to have developed treatment failure (7.8 per 100
person-years). A total of 253 patients changed at least one drug after failure (51.6 per 100
person-years). There was no difference between patients from high- and low-income countries.
Advanced disease stage, a lowerCD4 count and a higher HIV viral load were associated with a
higher rate of treatment modification after failure. Compared with patients from low-income
countries, patients from high-income countries were more likely to change two or more drugs
(67%vs. 49%; P=0.009) and to change to a protease-inhibitor-containing regimen.[20]

A hospital based retrospective cross sectional study done in Raichur, India assessed 3510 patient
records and (14.8%) of the patients had changed initial HAART regimen. About one third of the
patients (33%) were on AZT/3TC/NVP at the beginning of the ARV treatment and the rest were
on d4T/3TC/NVP (25%), TDF/3TC/NVP (23%) and AZT/3TC/EFV (14%), d4T/3TC/EFV
(3%), TDF/3TC/EFV (2%).Main reasons for the substitution to HAART regimens were co
morbidity (58.26%), followed by adverse drug reactions (ADR) (38.46%) and pregnancy
(3.28%).TB was the only major co-morbidity reported in this study. Among this (36.34%) were
cured of TB and rest (21.92%) were newly diagnosed with TB [21]
A study done in Côte d'Ivoire followed 2012 HIV infected adults initiating ART for a median
follow up time of 16.9 months. Overall, the rate of treatment modifications was 20.7/100 patient-
years (PY). The most common modifications were drug substitutions for intolerance
(12.4/100PY), pregnancy (4.5/100PY) and tuberculosis (2.5/100PY). The rates of intolerance-
related substitutions were 17.9/100PY for stavudine, 6.3/100PY for nevirapine, 3.9/100PY for
Zidovudine and 0.1/100PY for Efavirenz [22].

Longitudinal observational study in Kenya analyzed 1286 patients. The initial ART regimens
were primarily d4T/3TC/NVP (62.1%). Median ART duration was 350 days (11.6 months). ART
switches occurred in (54.5%) patients. Concurrent ART-related toxicities (40.6%) and
tuberculosis treatment interactions (28.1%) were the most frequent reasons for ART switch [23].

A Hospital based study conducted in Dessie assessed 122 patients who switched initial ART
regimen. The most frequent prescribed first regimens before switch were AZT/3TC/EFV (36%),
AZT/3TC/NVP (27%), d4T/3TC/EFV (19%) and d4T/3TC/NVP (18%). Toxicity (66%)
followed by co-morbidity (14%) and planning pregnancy (11%) were the most common reasons
for modification of ART. The main toxicity was anemia (52%) and peripheral neuropathy
(9%).Among these patients 8% of the patients had changed their regimen for a second time [24].

In a study done in Mekelle hospital assessed 105 patients’ records. About 20 % of the study
subjects had changed their initial ART regimen. In 71.4% of the cases the reason for change was
attributable to toxicity, with ZDV being the most dominant drug. Treatment failure and
pregnancy accounted for14.3% and 9.5%, respectively. Little more than half (54.3%) were
initiated on ZDV/3TC/NVP followed by 12.4% TDF/3TC/NVP and 11.4% TDF/3TC/EFV.
Anemia and rash were the most commonly reported ADR events [25].

A study done at Bedelle hospital assessed a total of 84 patient cards retrospectively. The most
common first line regimen, before the switch, was d4T/3TC/NVP (42.9%) and (d4T/3TC/EFV)
(25%). The main reasons for modification were toxicity, co morbidity, pregnancy, and 9
treatment failures. The main types of toxicities observed were peripheral neuropathy (31%),
anemia (27%), and rash (25.4%). d4T-base regimen had the highest hazard for ARV drug switch
[26].
1.4. Significance of the study
As a research, the primary merits of the study goes to the university academics. Since there were
few studies in the area, it gives a comprehensive starting point for more to assess the reasons
contributing for the change of ART regimen among patients with HIV/AIDS in different level of
health facilities in Ethiopia.

The study will design to identify the extent of ARV drug switch and the determinant factors
associated with these multiple switches. Furthermore, this study elucidates the patterns of ARV
drug switches in Nekemte Referal hospital.

Furthermore, the study helps for policy makers, baseline for other studies, guides other health
care providers to prescribe drugs correctly.
2. Objective

2.1. General objective

 To assess factors leading to antiretroviral regimen change among HIV/AIDS Positive
Patients in Nekemte Referral Hospital, East Wollega Zone, West Ethiopia

2.2. Specific objectives

 To identify the pattern of initial ART regimens and the subsequent changes

 To determine the proportion of ART regimen shift among patients whose initial ART
regimen had been changed

 To assess practice of ARV drug switch in adhering with the National and WHO guidelines
for use of ART

 To assess the relationship between patient characteristics and reasons for initial ART change.
3. Methodology

3.1. Study area and period

The study will be conducted from Aprill.28 to May 30/ 2017 in the ART Clinic of Nekemte
Referal Hospital which found in Nekemte Town, East Wollega Zone, Oromia region, West
Ethiopia. Nekemte town is located 333 km far away from West of Addis Ababa. It has a
population of 300,000 according to a census [27].

The area is well known by its coffee production. The climatic condition of the area is
‘Woinadega’ and it is found at 2080 m above sea level. According to the information from
Nekemte health bureau shows that there are 99 health institutions in the town, of which 41 are
private, 4 governmental (including one Referral hospital) and the rest are health institutions that
run by NGO’s. The hospital has a total of 307 staff of which 206 are health professionals of
different category. Presently there are about 2250 people are started on HAART in Nekemte
Hospital. There are 118 clients are on second line HAART regimen. The rest are still on the first
line HAART regimen. The personnel ART Clinic consisted of one monthly rotating general
practitioner, 2 consulting internists, 2 nurses, 2 data collectors, 6 adherence supporters and one
patient assistant. It has also a separate ART pharmacy with 1 pharmacists working full time.

3.2. Study Design

The study design will be a hospital based retrospective cross sectional study.

3.2. Source Population and Study Population

The source population will be constitute of all adult HIV infected patients who had been on
follow-up at the ART clinic of Nekemte Referal Hospital. The study population will include all
HIV infected patients initiated ART at Nekemte Referal Hospital that had experienced regimen
changing.
3.3. Inclusion and Exclusion Criteria
Inclusion criteria:

 Patients on follow up in the ART clinic who had undergone at least one ART regimen
switching until the study period.

 Adult HIV/AIDS patients 18 years old and above

 Patients receiving ARVs for at least 6 months at the beginning of the study period

 Patients receiving ARVs solely from Nekemte Referal Hospital ART pharmacy.

Exclusion criteria:

 Patients with incomplete information

 Patients with less than 6months on ART regimen.

3.4. Sample Size Determination and Sampling Technique

The sample size of the study is determined based on the calculating formula of (Yemane, 1967)
cited in Israel, 1992 that provides a simplified formula to calculate sample sizes.

n= N/1+N (e) 2
Where:

n= Sample size

N= Population size

e= Level of precision/sampling error

Total population (N) = 2250(current on ART)

95% confidence level and

e = 5% the level of precision is 0.05

There for the sample size of the study calculated as follows

n= N/1+N (0.05)2 = 2250/ 1+2250(0.05)2 = 2250/6.54 = 338.9 = 344

3.5 Sampling Procedures

The recorded list of patients who had been on HAART regimen is used as a sampling frame.
From a total of 2250 patients who had been on HAART regimen 344 patients will be included by
systematic random sampling method. But there are only 118 patients who changed their initial
regimen. Therefore, there are 118 patient who changed their initial regimen will be selected by
census method.

3.6. Study Variables

3.6.1. Independent Variables

 Socio-demographic characteristics: Age at initiation, Sex, Marital status, Educational status.

 Disease related variables: Baseline WHO stage, Base line CD4, and Baseline weight.

 ART related variables: Types of initial regimen

3.6.2. Dependent Variables

 Reasons for change

3.7. Data Procedure and Management

3.7.1. Data collection procedure

Data collection format (Annex I) is developed based on the objectives of the study. It contained
socio-demographic, clinical information and ART information such as, CD4 count, WHO stage,
initial regimen, date on which treatment was started, date of ARV drug switch, duration of initial
ARV therapy before first switch, regimen switched to, and reason for changing the ART. The
types of toxicity and treatment failure reasons were included. If there was ARV drug switch for
the second and third time it was recorded in a similar manner.

3.7.2. Data Collectors Recruitment and Training

Two pharmacists working in the ART pharmacy will be recruited and trained for one day each
about the methods of data collection prior to the start of actual data collection.
3.7.3. Data Quality Assurance/Control

To ensure data quality, the data collectors will be trained by the principal investigators for one
day each. The data collection format will be pre-tested in 5% of the sample size to check for
appropriateness of the data collecting instrument. Confusions and clarity found during the
process of pre-test will be corrected and modifications will be made accordingly. The principal
investigator has made frequent checks on the data collection process to ensure the completeness
and consistency of the collected data.

3.8. Data Analysis Procedures

The data will be cleaned for inconsistencies and missing values. The cleaned data are then coded
and entered into Statistical Package for Social Sciences (SPSS) version 20. Quantitative
Descriptive statistics is generated to meet the objective of the study. The categorical variables are
described using frequency tables and figures.

3.9. Ethical considerations

Prior to study initiation, ethical clearance will be obtained from Jimma University, School of
Pharmacy ethical review committee. In addition, permission will be sought from the Nekemte
Referal hospital medical director to conduct the study. Only numerical identifications are used as
a reference. Confidentiality and anonymity of subject is maintained by not recording identifying
details, such as name or any other personal identifiers. No disclosure of any name of the patients,
the healthcare provider or drug product is made in relation to the finding.
3.10. Operational Definitions
ABC based regimen: regimen containing Abacavir as one of the NRTI backbones and may have
different NNRI or PI bases.

Adherence difficulty: it is inability to achieve 95% adherence level to the ART medications
due to patient inconveniences in relation to pill burden, frequency of administration and other
patient related behaviors.

Antiretroviral drug switch/change: it is the change of one or two ARV drugs from the initial
drug regimens.

AZT based regimen: regimen containing Zidovudine as one of the NRTI backbones and may
have different NNRI or PI bases.

Co morbidity: is defined as the occurrence of one or more additional disorders which are on
drug therapy with HIV/AIDS simultaneously (TB, diabetes, hypertension)

d4T based regimen: regimen containing Stavudine as one of the NRTI backbones and may have
different NNRI or PI bases.

TDF based regimen: regimen containing Tenofovir as one of the NRTI backbones and may
have different NNRI or PI bases.

Toxicity: is defined as the occurrence of adverse events such as diarrhea, nausea, vomiting,
anemia, rash, fatigue, peripheral neuropathy, lipodystrophy, metabolic disturbances, CNS
abnormalities or any other unwanted effect related to HAART.

Treatment failure: is defined as either occurrence of new opportunistic infection (TB,

candidiasis, pneumonia, herpes simplex, toxoplasmosis, etc.), immunological failure (a drop of
CD4 cell count below baseline pretreatment level) or virologic failure (a virological rebound
after complete suppression).
4. Work plan and budget breakdown

4.1 Work plan

Table 1work plan

S.N Activities Time in Months, 2016/2017

Sep
Oct.

Nov.

Dec

Jan.

Feb

Mar

Apr

May

Jun
1 proposal development and presentation
3 For Approval and ethical clearance
4 Recruiting and Training of data
collectors and supervisors
5 Census of study population
6 Pretest questionnaires

7 Actual data collection

8 Data entry, cleaning & Data analysis

9 Writing results and discussion

10 Preparation of first draft and submission

to advisors
11 preparation and submission of second
draft
12 3rd draft preparation and submission

13 Presentation of findings to Wollega

university
14 Paper defense and result Dissemination
4.2 Budget breakdown

Table 2 .Budget Break Down

S.N Budget category Number of Unit price Number Total Remark

persons/unit (Birr) of days price

1 PERSONAL
1.1 Principal investigator 1 90.00 15 1350.00
1.2 Supervisor 1 90.00 10 900.00
1.3 Data collectors 8 58.00 10 4640.00
1.4 Secretary work 1 70.00 5 350.00
1.5 Questionnaire translator 2 70.00 1 140.00
Subtotal 7380.00
2 Training
2.1 Data collectors 8 58.00 1 464.00
2.2 supervisor 1 90.00 1 90.00
2.3 Trainer 1 90.00 1 90.00
Sub total 644.00
3 Tea/coffee for training 10 15.00 1 150.00
4 Transport 1 300.00 2 600.00 From
Jimma to

Subtotal 750 Nekemte

5 Stationary materials unit Price/ unit Total Total

5.1 Note book number 10.00 unit
10 price
100.00
5.2 Pen number 5.00 10 50.00
5.3 Pencil number 2.00 10 20.00
5.4 Staples Pack 5.00 10 50.00
5.5 Pencil sharpener number 5.00 10 50.00
5.6 Pencil Eraser number 2.00 10 20.00
Sub total 290.00
6. Printing and duplication
6.1 Semi structured pages 1.00 1000 1000.00
questionnaire copy for
6.2 Semi
censusstructured pages 2.00 2 4.00
questionnaire print
6.3 Questionnaire photocopy pages 1.00 1500 1500.00
6.4 Questionnaire printing pages 1.00 5 5.00
6.5 Proposal print pages 2.00 180 360.00
6.6 Final Thesis print pages 2.00 240.00 480.00
Sub total 3349.00
All total 12413.00
10% contingency 1241.3
G. Total 13,754.30
References:
1. F. Dabis, M.L.Newell. HIV drugs for treatment and for prevention. Lancet 2010: 375(9731):
2056-7.
2. FJ. Palella, KM. Delaney, AC. Moorman, et al. Declining morbidity and mortality among
patients with advanced human immunodeficiency virus infection. HIV Outpatient Study
Investigators. N Engl J Med1998:338 (13):853–60.
3. T.Mitiku. A. Ahmed. D. Ydeta. Determinants of Mortality among HIV Positives after
Initiating Antiretroviral Therapy in Western Ethiopia, ISRN AIDS 2013: Article ID 491601.
4. D. Ashebir. Mitigating the Impact of HIV/AIDS in Teacher Training Institutions: Analyzing
the Response in Ethiopia, UNESCO IICBA Newsletter2008; 10 (6) No. 1.
5. NH.Melroe, J. Kopaczeski, K. Henery, et al. Lipid abnormalities associated with protease
inhibitors. J assoc nurses AIDS care1999; 10(2):22-30.
6. MA. Chesney, M.Morin, L. Sherr. Adherence to HIV combination therapy. Socsci Med. 2000;
50 (5):1599-1605.
7. M.Thomson. Antiretroviral Treatment of Adult HIV Infection. JAMA 2010: 304(3): 321-333.
8. Food, Medicine and Health Care Administration and Control Authority (FMHACA). (2014).
Standard Treatment Guidelines For General Hospital. 3rd edtion.Addis
Ababa.Ethiopia.FMHACA.

9. Wilkin, T., Marshall Glesby, & Gulick, R. M. (2006). Switching Antiretroviral Therapy Why,
When and How. Journal of Acquired Immune Deficiency Syndromes, (12), 782–9.

10. Jima, Y. T., Angamo, M., & Wabe, N.-R. (2013). Causes for antiretroviral regimen change
among HIV/AIDS patients in Addis Ababa, Ethiopia. Tanzania Journal of Health Research,
15(1), 1–9.

11. World Health organization (WHO). (2013a). Global update on hiv treatment:results, impact
and opportunities,breif summary.Kuala Lumpur ,Malaysia:WHO

12. World Health organization (WHO). (2013b). Consolidated guidelines on the use of
antiretroviral drugs for treating and preventing HIV infection: recommendations for a public
health approach.Geneva, Switzerland:WHO.

13. Katabira, E., & Oelrichs, R. (2007). Scaling up antiretroviral treatment in resource-limited
settings: successes and challenges. AIDS (London, England), (21 Suppl 4), 5–10.

14. Petersen, M. L., Laan, M. J. van der, Napravnik, S., Eron, J. J., Moore, R. D., & Deeks, S. G.
(2008). Long term consequences of the delay between virologic failure of highly active
antiretroviral therapy and regimen modification. AIDS, October 18(22(16)), 2097–2106.

15. WB. Park, PG. Choe, SH Kim, JH. Bang. et al. Early modification of initial HAART regimen
associated with poor clinical outcome in HIV patients. AIDS Res Hum Retroviruses 2007; 23(8):
794–800.
16. S. Hendrickson, LP. Jacobson, GW. Nelson, et al. Host genetic influences on highly active
antiretroviral therapy efficacy and AIDS free survival. J Acquire Immune Defic Syndr. 2008; 48
(3):263-71.

17. Demessie, R., Mekonnen, A., Amogne, W., & Shibeshi, W. (2014). Knowledge and
adherence to antiretroviral therapy among adult people living with HIV / AIDS at Tikur Anbessa
Specialized Hospital , Ethiopia.International Journal of Basic & Clinical Pharmacology,3(2),
320–330.

18. Elzi, L., Marzolini, C., Furrer, H., Ledergerber, H., Cavassin, M., Hirschel, B.et al. (2010).
Treatment modification in human immunodeficiency virus-infected individuals starting
combination antiretroviral therapy between 2005 and 2008. Arkives of Internal Medicine,
11(170(1)), 55–65.

19.Cesar, C., Shepherd, B. E., Krolewiecki, A. J., Fink, V. I., Schechter, M., Tuboi, S. H. et al.
(2010). Rates and reasons for early change of first HAART in HIV-1-infected patients in 7 sites
throughout the Caribbean and Latin America. PloS One, 5(6)

20. Zhou, J., Li, P. C. K., Kumarasamy, N., Boyd, M., Chen, Y. M. a, Sirisanthana, T.et al.
(2010). Deferred modification of antiretroviral regimen following documented treatment failure
in Asia: Results from the TREAT Asia HIV Observational Database (TAHOD). HIV Medicine,
11(1), 31–39.

21. Sandeep, B., Vansant, R. C., Raghunandan, M., Arshad, M., & Suresh, B. S. (2014). Factors
influencing the substitution of antiretroviral therapy in human immunodeficiency virus/acquired
immunodeficiency syndrome patients on first line highly active antiretroviral therapy. Asian
Journal of Pharmaceutical and Clinical Research, 7(5), 117–120.

22. Messou, E., Anglaret, X., Duvignac, J., Konan-N’dri, E., Komena, E., Gnokoro, J.et al.
(2010). Antiretroviral treatment changes in adults from Côte d’Ivoire: the roles of tuberculosis
and pregnancy. AIDS (London, England), 24(1), 93–9.

23. Hawkins, C., Achenbach, C., Fryda, W., Ngare, D., & Murphy, R. (2007). Antiretroviral
durability and tolerability in HIV-infected adults living in urban Kenya. Journal of Acquired
Immune Deficiency Syndromes , 45(3), 304–310.

24. Mulugeta, A., & Chane, T. (2012). Cause of Antiretroviral Drug Changes Among Patients on
Antiretroviral Therapy At the Art. International Journal of Pharmaceutical Sciences and
Research, 3(1), 120–125.
25. Bayou, T., Woldu, M., G.Meskel, G., & Mezgebe, H. (2014). Factors determinant for change
of initial antiretroviral treatment regimen among patients on ART follow-up clinic of Mekelle
Hospital, Mekelle, Ethiopia. International Journal of Basic & Clinical Pharmacology, 3(1), 44.

26.Mekonnen, K. Y., & Molla, K. G. (2014). Reason for Regimen Change Among HIV Patients
on Initial Highly Active Antiretroviral Therapy in Bedele. Journal of Biotechnology and
Biosafety, 2(4), 116–122

27. NTHB, 2003. Census by Nekemte Town Health Bureu

Annex: Data Collection Format
Wollega University, Pharmacy Department
The tools will be used to collect data for a research with the title “Assessment of Factors of
Antiretroviral Regimen Change among HIV/AIDS Positive Patients in Nekemte Referral
Hospital, East Wollega Zone, West Ethiopia"
Part I: Socio demographic Characteristics
0 Card No…
1
0 Age…………………………………………………in years
2
0 Sex: Male Female
3
0 Age on ART initiation:………………………………………..
4
0 Years/months on ART……………………………………......
5
0 Family size:…………………………………………………….
6
0 Marital status:Single Married Separated Widow
7
0 Educational status: No formal education Primary school education
8 Secondary school education Higher institute education
0 Residence: Urban Rural
9
PartII: Clinical and immunological Characteristics
0 Weight: During initiation of ART…..Before ART switch……………Latest weight ………
1
0 Base line CD4 count on initiation of ART ……Before ART switches …… latest CD4……
2
0 WHO clinical stage on initiation of ART……. Before ART switch………..latest stage……
3
0 Baseline viral load (VL)……VL before initial ART switch….. Latest viral load (VL)……..
4
0 Initial ART regimen……………… Regimen switched to……………………___________

5
0 TB treatment : Yes No__________________________

6
0 OI prophylaxis: Yes No if yes Cotri- moxazole Isoniazid
Other medication………………………………
7
Part III: Reason(s) for ART Switch
0 Toxicity:
Anemia Rash Nausea Headache amenorrhea
1 Peripheral neuropathy Hepatotoxicity Diarrhea CNS toxicities
Renal failure Lipodystrophy Abdominal-pain GI irritation Fatigue
Dyslipidemia Jaundice
Other toxicity (specify)………………………………………………
0 Treatment Failure:
Immunologic failure Peak CD4…………CD4 during change...................
2 Clinical failure Clinical finding(s)………………………………………………….
Virologic failure Baseline VL……………….. VL during change……………….
0 Pregnancy ____ Adherence difficulty
_______________________________________________
3
0 Co morbidity Type of comorbidity…………………………..
5
0 Stock out_________ Other reason (specify)……………………….