dc.contributor.author | Nyakiba, Jarred O | |
dc.date.accessioned | 2013-06-03T15:38:53Z | |
dc.date.available | 2013-06-03T15:38:53Z | |
dc.date.issued | 2010 | |
dc.identifier.citation | Master of Pharmacy in Clinical Pharmacy | en |
dc.identifier.uri | http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/28884 | |
dc.description.abstract | Efavirenz is a non-nucleoside reverse transcriptase inhibitor specific against HlV-l that is used
3.S a component of HAART in combination with two NRTls at an adult dose of 600mg daily.
Rifampicin is a semi-synthetic derivative of rifamycin that is administered with other anti-TB
drugs for the first line management of active TB at an adult dose of 300-600mg per day.
Rifampicin induces the cytochrome P450 enzyme system in the liver which also metabolizes
efavirenz resulting in decreased levels of efavirenz. When this is coupled with the large interpatient
and intra-patient variability in efavirenz plasma concentrations, it could lead to subtherapeutic
concentrations hence treatment failure or toxic concentrations hence adverse
effects. The aim of this study was to determine the plasma levels of efavirenz and the treatment
outcomes in Kenyan HIV -TB co-infected patients receiving concomitant Anti-TB therapy and
ART at Kenyatta national hospital.
The study was designed as a concurrent descriptive cohort study. HIV-TB co-infected Kenyan
patients attending the comprehensive care centre of Kenyatta National Hospital who met the
study inclusion criteria were recruited into the study. Following approval by the Kenyatta ..
National Hospital ethics and research committee and a written informed consent. 28 HIV -TB
co-infected patients of Kenya origin were recruited into the study from January 2010 to March
2010. Patient demographics, history, baseline data and treatment outcomes were obtained by
medical record review. Plasma concentrations of efavirenz were determined by reverse phase
high performance liquid chromatography with UV detection (HPLC-UV). Two blood samples
were obtained from each subject on two separate occasions separated by a minimum of 2
weeks.
Data analysis was performed by SPSS version 12.0 software. Descriptive and exploratory data
analysis was carried out for each variable. Intra and inter-patient variability was determined
using the coefficient of variation. Comparison of plasma concentrations at first and second
occasions and with different variables was done using various nonparametric tests, Post hoc
multiple comparison and Spearman's rho correlation. Multivariate data analysis was done by
general linear regression (repeat measures).
The median plasma concentrations (Range) at the first and second sampling occasions were
13.17 (0.04 - 52.48) ug/ml and 10.66 (3.54 - 57.61) ug/ml. On l" sampling one patient (3.7 %)
had sub-therapeutic plasma EFV concentrations «1 ug/ml) while only one patient (3.7 %) had
therapeutic plasma EFV concentrations (1-4 ug/ml). A majority of patients (92.6 %) had toxic
plasma EFY concentrations (>4 ug/ml). Out of these 25 patients with toxic levels, 68 % had
levels between 4 and 20 ug/ml while 32 % had levels above 20 ug/ml. On the second sampling
occasion, no patient had sub-therapeutic plasma EFY concentrations while only one patient
(4.3 %) had therapeutic plasma EFV concentrations. A majority of patients (95.7 %) had toxic
plasma EFY concentrations. Out of these 22 patients with toxic levels, 72.7 % had levels
between 4 and 20 ug/ml while 27.3 % had levels above 20ug/ml.
A high intra-patient variability of 32.5 % was observed and a high inter-patient variability of
77.8 % on first and 86.4 % on second sampling was observed. Females consistently had higher
efavirenz plasma concentrations than male patients though this was not statistically significant.
Bodyweight was a statistically significant factor with patients weighing less than 60 kilograms
having higher EFY levels than those weighing >=60 kilograms. Ethnicity was also a significant
factor with higher efavirenz levels in the Kamba compared to Kikuyu, Kisii, Luhya and
Kalenjin being demonstrated. Multivariate analysis of bodyweight, ethnicity and gender
showed that they were not statistically significant determinants of efavirenz levels and a large
study is required to assess the contribution of these variables to efavirenz levels.
Treatment outcomes were difficult to assess irf this study. Although there was a statistically
significant difference in the CD4 counts, this was not correlated to the high efavirenz levels.
There were 24 episodes of adverse effects in 28 patients implying that nearly every patient
would experience an adverse effect during treatment. The prevalence of adverse effects
increased on onset of anti- TB therapy and gradually reduced. Skin adverse effects were the
most common followed by drug induced hepatitis. Gastrointestinal adverse effects presented
early while neurological and metabolic adverse effects presented later.
,
Contrary to the expectation that efavirenz levels would be lower m patients recerving
rifampicin, a large proportion of Kenyan HIY -TB co-infected patients have toxic efavirenz
levels and high rates of adverse effects were observed in these patients. Clinicians should
therefore be particularly vigilant for signs of toxicity. A priori dose reduction in native African
patients, a pharmacogenetic-therapeutic drug monitoring approach to individualised dosing and
a prospective clinical dose optimization and treatment outcome study in Kenyans and indeed
native Africans are immediately required. | en |
dc.language.iso | en | en |
dc.publisher | University of Nairobi | en |
dc.title | Efa virenz levels and treatment outcomes in Kenyan HIV-TB co-infected patients at Kenyatta national hospital | en |
dc.type | Thesis | en |
dc.description.department | a
Department of Psychiatry, University of Nairobi, ; bDepartment of Mental Health, School of Medicine,
Moi University, Eldoret, Kenya | |
local.publisher | Department Of Pharmaceutics And Pharmacy Practice. | en |