|
Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996 EISSN: 1596-9827
Vol. 9, Num. 1, 2010, pp. 1-10
|
Tropical Journal of Pharmaceutical Research, Vol. 9, No. 1, 2010, pp. 1-10
Research Article
Treatment Outcomes in Patients Receiving
Combination
Antiretroviral Therapy in Central Hospital, Benin City, Nigeria
Kenneth
A Agu*, Uche M Ochei, Azuka C Oparah and Obialunamma U Onoh
1Department of Clinical Pharmacy and Pharmacy
Practice, University of Benin, Benin City, 300001 Nigeria; 2 West
African Postgraduate College of Pharmacists, Lagos, Nigeria.
*Corresponding author: E-mail: kenagpharm@yahoo.com
Received: 11 April 2009
Revised
accepted: 10 November 2009
Code number: pr10001
Abstract
Purpose:
This study
investigated mortality rate, early CD4 responses, pattern of ARVs substitutions
and medication adherence of HIV-infected patients on first-line triple
combination antiretroviral therapy (ART) in Central Hospital, Benin City, Nigeria.
Methods: A retrospective assessment of 196 HIV-infected
patients on first-line combination ART regimens was performed following 18
months of therapy. Medication adherence assessment of a 69-patient follow-up
target group was based on a study-specific questionnaire. Paired sample t-test
and simple linear correlation were used to test the association of the CD4-cell
counts at different time intervals. Kaplan-Meier model was used to assess
survival functions while log-rank test was applied to assess statistical
difference at 95 % confidence interval (CI). Mean age of participants was 33.6
years (95 % CI, 32.1 - 35.2; 67.9 % were females.
Results: At ART
initiation, 27.0 % were at WHO clinical stage II, 47.0 % at stage III.
Mortality rate (N = 196) was 20.3 deaths per 100 patient-months; 31.6
% occurred in < 30 days while 52.6 % occurred post-120 days of treatment.
The mean CD4-cell count (cells/mm3) at ART initiation was
179.2 which increased to 328.5 at 3 months, 325.6 at 6 months, 357.4
at 12 months, and 366.7 at 18 months, (p < 0.01). Patients
started on stavudine-based or efavirenz-based regimens were considerably more
likely to have that drug substituted, compared to patients started on
zidovudine-based or nevirapine-based regimens. The level of adherence reported
after 18 months on ART was 73.8 %.
Conclusion: In this
setting, patients receiving ART showed significant improvements in
CD4-cell status but adherence level was relatively poor. Patients were more
stable on zidovudine-based or nevirapine-based regimens than on stavudine-based
or efavirenz-based regimens. Early mortality rate was high, indicating a need
for early interventions.
Keywords: Antiretroviral
therapy; HIV/AIDS; Mortality; Therapy outcomes, Nigeria
INTRODUCTION
Epidemiological
surveillance of HIV/AIDS in Nigeria showed an increasing prevalence from
0.000001% in 1986 to 0.22 % in 1987, 1.8 % in 1991, 3 % in 1992, 3.8 % in 1993,
4.5 % in 1996, 5.4 % in 1999, and 5.8 % in 2001 [1]. The 2003 surveillance
recorded a slight drop to 5.0%; this translates to 3.8 million Nigerians living
with HIV - about 20 % of the HIV/AIDS burden of the African continent and 10 %
of the global HIV/AIDS burden. There was a further slight drop in 2005 to 4.4 %
[2,3]. The epidemic in Nigeria can be described as heterogeneous,
with various communities in different stages. Young people (age 15 – 24 years)
constitute a large proportion of those infected, while younger ages, primary
and secondary education levels, were associated with higher risk of HIV
infection with 5.9 % and 5.4 % prevalence, respectively [1,4]. The problem of
HIV/AIDS in Nigeria further compounds the nation’s poor health indices. The Nigerian
antiretroviral therapy (ART) guideline for initiating ART in adults and
adolescents is dependent on WHO
clinical staging and availability of CD4-cell count testing [2], and endorses
largely the WHO guideline on ART initiation.
In a study by Bolton-More et al, the
results showed that patients starting a zidovudine-based regimen or
efavirenz-based regimen were considerably more likely over time to have that
drug substituted, compared with patients starting a stavudine-based regimen or
nevirapine-based regimen respectively [7]. In
another study at Chiradzulu District of Malawi by Ferradini et al, a simplified
HAART programme was scaled up and survival indicators - CD4 count evolution,
virological response, and adherence to treatment - analyzed in adults who
started HAART six months or more before the analysis. At follow-up (median 8.3
months), 74 % were still on HAART, 19 % had died, 7 % were lost to follow-up,
and 0.5 % discontinued treatment. The study showed that WHO stage IV, male sex,
and baseline CD4 count lower than 50 cells per mμL were independent
determinants of death in the first 6 months. At 12 months, the probability of
individuals still in care was 0.76 and the median CD4 gain was 165 cells per
mμL. Of several indicators measuring adherence, self-reported poor
adherence (< 80%) in the past 4 days was the best predictor of detectable
viral load [8]. Recent studies demonstrated the long-term effectiveness of
antiretroviral therapy (ART) in a developing country urban setting [9,10].
These studies suggest the importance of monitoring ART patients more closely
over the first year, even if six-month immunological and virological responses
appear to be good.
The
effectiveness of HIV/AIDS management depends critically on the efficacy of the
antiretroviral drugs (ARVs) against the virus and adherence to medications.
Recent studies indicate that triple combination ART regimens have proved
efficacious in industrialised countries in response to HIV/AIDS but the
prolonged effectiveness of ART in a developing countries is not well
established. Furthermore, the efficacy of ARVs might not be the same for some
HIV strains present in Africa [7-9]. The high cost of ART intervention,
complicated procedures, inadequate infrastructures for following up patients
and delivering medicines regularly, stigma and discrimination make access to
care and support more difficult for HIV-infected patients. Misconceptions,
cultural beliefs, poor socio-economic indices and ignorance are among the
factors that could constitute the greatest challenge to wide acceptance and
adherence to ART in Africa. Since adherence is the cornerstone of successful
ART [11-16], there is a need to appraise the treatment outcomes of ART
interventions against these factors which are considered as obstacles to
mounting concerted ART programmes in Nigeria.
The evaluation of the effectiveness of
combination ART regimens in the management of HIV positive patients in Nigeria is
particularly important because the supporting efficacy data are scanty. This
study aims to document the evidence of ART efficacy in Edo State, Nigeria. Edo, one of the 36 States in Nigeria, has a population of over 3.2 million and an estimated
number of >140,000 people living with HIV. About 70,000 people in this state
are in need of HIV comprehensive care services [3,5,6]. The objectives of this
retrospective investigation were, therefore, to describe early CD4-cell response
and mortality rate of HIV-infected patients on triple combination ART after 18
months, to assess the patients’ pattern of ARVs substitution within the
first-line ART regimens, and to assess medication adherence of those patients
active on treatment after 18 months period.
METHODS
Study design
A retrospective assessment of ART patients was
performed using routinely collected clinical and outcome data from the
patients’ hospital records. Medication adherence of patients active on
treatment after 18 months of ART was
prospectively assessed using the self-report adherence method.
Setting
This
study was carried out in Central Hospital Benin, a secondary public health care
facility in Benin City, Nigeria which offers comprehensive HIV care services,
starting October 2005. We obtained administrative approval from the management of the hospital and informed
consent from the study participants.
Population/Sample
The study sample was a group of
196 patients, who enrolled and commenced ART 1st October to 31st
December, 2005. A sub-sample of the
HIV-positive patients that were active on treatment as of October 12, 2007 was
selected for a follow-up medication adherence. The sample size for this
subgroup was statistically determined from the population to be 64 out of 196
and hence a target of 69 patients was followed up.
Inclusion/Exclusion criteria
All
HIV positive patients who were enrolled and commenced ART within the study
period, and refilled their prescriptions at the Pharmacy Department of the facility
were included. Only the patients
indicated above who were active on treatment as at October 12, 2007 were
included for medication adherence
assessment. Participants
consented to their inclusion. All those
patients who did not meet the required criteria or give informed consent were
excluded from the study.
Data collection
An
unobtrusive technique was used to collect relevant data from the manually
maintained records of the 196 participants using a structured instrument.
Twenty patients were used in the pilot study for this aspect of the
investigation. A study-specific questionnaire was administered to the
sub-sample of 69 patients. This was done over a period of three and half months
as this sub-sample had varying medication refill appointment dates. Similarly,
5 patients were involved in the pilot study prior to the main data collection. A researcher and two trained assistants
administered the survey instruments.
Data analysis
The
data were analyzed using SPSS version 10. Paired sample t-test and
simple linear correlation were used to test the association of the CD4-cell
counts at different time intervals. Kaplan-Meier model was used to assess
survival functions stratified by baseline CD4-cell count and WHO clinical
stage, and the log-rank test was used to assess statistical difference among
groups (for equality of
survival distributions). Mortality rates
overall, at < 30 days, 30 – 60days, 61 – 120 days and > 120 days were
determined using the Life Table. All reported P-values were 2-sided, and P <
0.05 was used to determine statistical significance.
RESULTS
Socio-demographic
characteristics of patients
Of
the 196 study participants, 194 (99.0 %) were treatment-naïve while 2 (1.0 %) were
already receiving ART prior to enrollment. The mean age of the 196 patients at
initiation of antiretroviral treatment was 33.6 years (95 %CI, 32.1 - 35.2).
Other socio-demographic characteristics of the patients are presented in Table
1.
Table 1: Socio-demographic characteristics
of patients
Characteristics
|
Frequency
(N=196)
|
%
|
SEX
|
Male
|
63
|
32.1
|
Female
|
133
|
67.9
|
AGE
|
≤15
|
9
|
4.6
|
16-25
|
25
|
12.8
|
26-35
|
79
|
40.3
|
36-45
|
62
|
31.6
|
46-55
|
16
|
8.2
|
≥56
|
5
|
2.5
|
MARITAL STATUS
|
Single
|
60
|
30.6
|
Married
|
104
|
53.1
|
Widow(er)
|
22
|
11.2
|
Divorced/Separated
|
10
|
5.1
|
EDUCATIONAL STATUS
|
None
|
11
|
5.6
|
Primary
|
69
|
35.2
|
Secondary
|
70
|
35.7
|
Post
Secondary
|
31
|
15.8
|
Not
indicated
|
15
|
7.7
|
OCCUPATIONAL STATUS
|
Unemployed
|
72
|
36.7
|
Employed
|
25
|
12.8
|
Self-employed
|
49
|
25.0
|
Not
indicated
|
44
|
22.4
|
Retired
|
1
|
0.5
|
Student
|
5
|
2.6
|
Patients’
baseline clinical characteristics
Baseline
weights were available for 178 patients (90.8 %) with a mean value
of 56.6 kg while 18 (9.2 %) had no documented baseline weights; the median
CD4-cell count at initiation of antiretroviral treatment was 101 (IQR, 35 -
206) cells/mm3. Those that were ART-eligible and initiated treatment
based exclusively on the CD4-cell count result was 142 (72.4 %), while a few
(21.4 %) were based exclusively on the clinical staging. Pre-treatment
medication adherence counselling was given to 193 (98.5 %) patients while 3
(1.5 %) had no documentation of this service (Table 2).
Table 2: Baseline
clinical characteristics
Characteristics
|
Frequency (N=196)
|
%
|
WHO
Clinical Stage
|
I
|
42
|
21.4
|
II
|
53
|
27.0
|
III
|
92
|
47.0
|
IV
|
6
|
3.1
|
Not
indicated
|
3
|
1.5
|
CD4-cells
Count (cells/mm3)
|
<10
|
21
|
10.7
|
10–49
|
44
|
22.4
|
50–100
|
31
|
15.8
|
101–200
|
46
|
23.5
|
201–350
|
25
|
12.8
|
>350
|
26
|
13.3
|
Not
indicated
|
3
|
1.5
|
Functional
Status
|
Working
|
147
|
75.0
|
Ambulatory
|
35
|
17.8
|
Bed-ridden
|
5
|
2.6
|
Not
indicated
|
9
|
4.6
|
Experience
with first-line antiretroviral drug regimens
The
196 patients were started on antiretroviral first-line drug regimen and
remained on it until the last medication refill visit in the Pharmacy records.
Of 196 patients initiating ART, 40.8 % were placed on
stavudine+lamivudine+nevirapine, 46.9 % on zidovudine+lamivudine+ nevirapine,
7.7 % on zidovudine +lamivudine+efavirenz, while 4.6 % were placed on
stavudine+ lamivudine+ efavirenz. There were no switches from first-line
regimens to second-line or salvage regimens.
Overall,
14.8 % patients had single-drug substitution of their nucleoside reverse
transcriptase inhibitors, 0.5 % had a two-drug substitution of nucleoside reverse
transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor
(i.e., “stavudine+nevirapine” substituted to “tenofovir+efavirenz”) while 5.1 %
had single-drug substitutions of their non-nucleoside reverse
transcriptase inhibitors. These substitutions were due to few cases of drug
intolerance, toxicity, or pregnancy, and many cases of undocumented
reasons. Of 45.4 % patients initiated with stavudine-based regimen, 15.7
% switched from stavudine to zidovudine. Additionally, 13.1 % of 54.6 %
patients initiated with zidovudine-based regimen switched from zidovudine to
stavudine. Out of 87.8 % patients receiving a nevirapine-based regimen, 3.5 %
switched to efavirenz (of which 33.3 % switched back to nevirapine),
while of 12.2 % patients starting an efavirenz-based regimen, 3.5 % switched
to nevirapine.
Survival
outcomes
As
of October 12, 2007, out of the total 196
patients, 19.4 % were documented to have died over 187
patient-months of follow-up (mortality
rate of 20.3 deaths per 100 patient-months); 38.8 % were active and still on
treatment at the facility, 6.6 % transferred out to other facilities; 3.0 %
stopped treatment on medical advice, of which 83.3 % were due to pregnancy and
16.7 % documented to have gone on drug holiday based on medical advice due to
high CD4-cell count. A total of 27.6 % of patients could not be followed up due
to logistic reasons while 4.6 % patients’ hospital case notes were missing and
could not be traced.
Mortality
in ART patients
The
actual causes of death in these cases were not documented. Of the 38 dead
patients having a baseline mean weight of 49.1 Kg and mean age of 36.0 years,
the baseline
median CD4-cell count at initiation of antiretroviral treatment was 44 (IQR,
7 to 85) cells/mm3. 2.6 % had no documented baseline CD4-cell count
but presented at stage IV. Of the dead cases, 81.6 % presented for treatment
at either stage II or III, while those that presented at WHO clinical stage
III,
63.2 %, were more than 3-fold higher than those that presented at WHO clinical
stage II (18.4 %); 7.9 % were stage I and 10.5 % were stage IV. In terms
of functional status, 63.2 % were either ambulatory (55.3 %) or bedridden
(7.9
%) at the time of presentation for treatment while 36.8 % were working.
The
mean treatment duration before death was found to be 282.5 (95 %CI,
243.2 to 321.9) days while the mortality rate was 20.32 deaths per 100
patient-months (Table 3).
Table 3: Mortality in ART patients
Time
interval |
Number
entering this interval |
Deaths |
Follow-up(patient-months) |
Mortality
rate(deaths per 100 patient-months) ±SD |
Overall
|
196
|
38
|
187
|
20.32±0.66
|
< 30 days
|
187
|
12
|
168
|
7.14±0.51
|
30–60 days
|
137
|
4
|
133
|
3.01±0.06
|
61–120
days
|
125
|
2
|
123.5
|
1.62±0.01
|
> 120 days
|
115
|
20
|
113.5
|
17.62±0.11
|
The
mean survival times before death for the ART patients with a baseline CD4-cell
Count of < 50 and 50–100 cells/mm3 were least for baseline stage
IV, being 528.5 and 351.0
days, respectively, but there was no
significant difference (p > 0.05) for both CD4-cell count categories for
baseline stages I – IV (< 50cells/mm3, p = 0.3866;
and 50–100cells/mm3, p = 0.4578). Considering the baseline
functional status, the mean survival times before death for the ART patients
working and ambulatory were also least for baseline stage IV, yielding 56.0 and 434.0 days respectively, but there was a significant difference (p < 0.05)
for the category working at baseline WHO clinical stage I – IV (p = 0.0296) while that of ambulatory patients
was not significantly different for baseline
WHO clinical stage I – IV (p = 0.1710).
Loss
to follow-up
Of
the 54 patients lost to follow-up, their baseline mean weight was 56.2 kg and
mean age was 30.8 (IQR, 25 - 37) years. The median CD4-cell Count at initiation
of ART was 142.5 (IQR, 50.5 – 296.0) cells/mm3. Of these patients,
61.1% had baseline CD4-cell Count > 100 cells/mm3 while 38.9 %
had baseline CD4-cell Count of ≤ 100cells/mm3 of which 25.9 %
were < 50 cells/mm3. That compared considerably better to the
baseline parameters for the death cases reported above. Those presented for
treatment at either stage I (33.3 %) or stage II (27.8 %) were 61.1 % while
35.2 and 3.7 % were at stages III and IV, respectively. For functional status,
90.7 % was reported to be working while 5.6 % were ambulatory and 3.7% were
bedridden. Of the 147 patients that had a working functional status, loss to
follow-up patients contributed 33.3 %.
The
mean duration of treatment before loss to follow-up was 392.3 (95 %CI, 350.8 to
433.7) days. Of 54 patients lost to follow-up, 24.1 % were lost to follow-up in
< 30 days of treatment, 7.4 % in 30 - 90 days, 1.8 % in 91-180 days and
66.7% post-180 days of treatment.
Patients
active on ART at the end of 18 months
Of
the 76 patients still on treatment, the baseline mean weight was 59.5 kg with a
mean age of 34.4 (IQR, 29 to 39.25) years and the median pre-treatment CD4-cell
Count of 113 (IQR, 37-190) cells/mm3. Of these, 52.6 % had baseline
CD4-cell Count > 100 cells/mm3 while 47.4 % had baseline CD4-cell
Count of ≤ 100 cells/mm3 of which 34.2 % were < 50 cells/mm3.
All the patients received pre-treatment medication adherence counselling. The
pre-treatment WHO Clinical staging of this category of patients comprised 15.8
% at stage I, 34.2 % at stage II, 50.0 % at stage III, and none was at stage IV
while the baseline functional status was 86.8 % working, 13.2 % ambulatory, and
none was bedridden.
CD4-cell
Count changes over time
The CD4-cell response analysis was limited to 186
patients who had a baseline CD4 measurement. The mean CD4-cell
count at ART initiation was 179.2 (95 %CI, 143.6 - 220.9) cells/mm3
and increased to 328.5 (95 %CI, 294.7 - 362.3) cells/mm3 at 3
months (80.3 % increase from the mean baseline value) among the 75 of 135 (55.6
%) active patients who had been enrolled long enough to have a
3-month measurement. This increased to 325.6 (95 %CI, 290.5 - 360.6)
cells/mm3 at 6months (78.7 % increase from the mean baseline value)
among the 62 of 118 (52.5 %) active patients enrolled long enough to
have a 6-month measurement. At 12 months, it increased further to
357.4 (95 %CI, 320.4 - 394.3) cells/mm3 (96.1 % increase from the
mean baseline value) among the 55 - 98 (56.1 %) active patients enrolled long
enough to have a 12-month measurement, and finally to 366.7 (95 %CI,
328.3 - 405.1) cells/mm3 at 18 months (101.2 % increase from the
mean baseline value) among the 66 of 76 (86.8 %) active patients enrolled long
enough to have an 18-month measurement. The
percent increase from the patients’ baseline CD4-cell Counts (cells/mm3)
at the different time intervals was significant at both 0.01 and 0.05
probability levels (p < 0.01) but there was no statistical difference
between the following pairs of CD4-cell Count measurements - at 3rd
and 6th month, 6th and 12th month, 12th
and 18th month (p > 0.05). The correlation of the CD4-cell Counts
measured at the different time intervals was found to be positive and
statistically significant at 0.05 probability level.
Medication
adherence
Of
the 69 patients (90.8 %) that were reached, out of those 76 patients still on
treatment, there were 65.2 % females and 34.8 % males. The age distribution of
the 69 patients reached at the time of assessment showed that a majority of them
(68.1 %) were between the ages of 26 and 45 years, 18.9 % patients were above
45 years while 13.0 % were below 25 years. A majority of the patients (55.1 %)
were married, 26.1 % were single while 17.4 % and 1.4 % of the patients were
widowed and either divorced or separated, respectively. Only 17.4 % had
post-secondary education while 79.7 % had either secondary school (42.0 %) or
primary school education (37.7 %). The greater percentage of patients (79.7 %)
were employed, including those that were self-employed while only a small
proportion were unemployed (11.6 %) and 7.2 % were students.
Of
the 69 patients, 89.9 % reported knowing the benefits of antiretroviral therapy
(of which almost all respondents, 98.4 % got it rightly stated) while 10.1 %
reported not knowing the benefits of ART. A majority of the respondents, 84.1
%, had a good knowledge of the importance of medication adherence; a few, 14.5
%, did not, while 1.4 % was not sure of this. The respondents reported a good
therapeutic relationship with the healthcare providers with a mean score of
88.4 %.
All
the 69 respondents reported receiving medication adherence counseling before
starting ART. On following the scheduled specific timing for taking the
medications, the respondents had a mean score of 64.1 % while the mean score
for taking the right drug in the right dose at the right frequency,
irrespective of the specific timing, was 83.5 %. Overall, the 69 respondents
recorded 73.8 % level of adherence to medications.
The
patients that reported not missing any dose of their medications were 35 (50.7
%) while 34 (49.3 %) had missed one or more pills (of which 30, or 88.2% of
them, missed 6 doses and less) in the previous two months. The occupation of
the respondents was associated with adherence (p = 0.00142) while educational
status of the respondents was not (p= 0.0971).
The
three most reported reasons for missed doses were: busy working or at school
(41.9 %), patient moved away from home or travelled (19.8 %), and forgetfulness
(14.0 %). Of the 69 respondents, 59.4 %
were taking one to three pills per day while 36.2 % were taking at least five
pills per day.
DISCUSSION
Analysis
of the demographic profile of the patients showed that a majority of those most
at risk of HIV infection were youths and the proportion of females in the
treatment group was more than two-fold greater than that of the males. This is
consistent with a recent study [3]. Almost all ART initiation among the
participants was done in line with the provision of the Nigeria ART guidelines
[2].
A
large proportion of the patients presented very late for treatment with very
poor baseline parameters such as CD4-cell count and WHO Clinical stage; for
example, half presented for treatment with WHO Clinical stage of either III or IV.
This finding supports the need for a rapid scale-up of counselling and testing
for early detection of asymptomatic cases in developing countries. The study finding is also consistent with
the results of Bolton-more et al, that patients starting a zidovudine-based
regimen or efavirenz-based regimen were considerably more likely over time to
have that drug substituted, compared with patients starting a stavudine-based
regimen or nevirapine-based regimen respectively [7]. The participants were stable on the first-line
regimen and none of the patients switched to the 2nd-line or 3rd-line
antiretroviral regimens.
The
proportion of the participants still on treatment at the end of 18 months
period was relatively low compared to the study findings of Ferradini et al [8]
while the number of fatal cases was similar but loss to follow-up was higher.
Mortality rate was high probably due to poor baseline parameters or late
presentation for treatment. The findings showed that a considerably high
percentage of patients with good CD4-cell response presented relatively early
for treatment at a relatively higher baseline CD4-cell Count, stage I or II and
better functional status, compared to the reported dead cases. Therefore,
relatively high baseline parameters with good adherence could be considered as
good prognostic factors.
In
this study, patients receiving ART showed significant improvements in
CD4-cells status at 3, 6, 12 and 18
months of antiretroviral therapy. This is consistent with recent studies [8-10]. Therefore, the early immunological response of
HIV-infected patients on ART after a period of 18 months was considerably good
in our setting. But mortality within the first 120 days of starting therapy was
high. Although many patients were ill at presentation, those who
survived past the first 120 days of therapy generally had good outcomes
thereafter, a phenomenon that has been observed among adults in
other developing-world settings [7].
As
has been described in other regions [7], the result showed that surviving
patients generally have very good CD4-cell responses. The average patient
in the cohort experienced a more than doubling of his or her
CD4-cell count in the first 18 months of ART. It was also observed that
follow-up CD4-cells measurements were not done every 6 months for all patients
eligible for repeat CD4-cell Count in accordance to the national ART guidelines
[2]. On the average, these follow-up CD4-cells measurements were repeated in
about two-third of the cases, hence the need for improvement in the adherence
to the national treatment guideline [2].
Adherence
to medication and lifestyle changes is a key factor to positive treatment
outcome in the therapy of HIV/AIDS and this presents a challenge to both
patients and healthcare providers [11-16]. The patients’ knowledge of the
benefits of ART and consequences of non-adherence of a majority was found to be
high and that might have enhanced medication adherence and possibly the
survival of patients on ART. From the result in this treatment centre, it can
be deduced that these patients were well educated and counselled on the basic
facts about ART before or after treatment initiation. The respondents also
reported a good therapeutic relationship with the healthcare providers which
are considered very essential for a successful adherence to medications.
Despite these and the fact that all the respondents were counseled on
medication adherence before starting ART, adherence was still found to be poor,
73.8%, compared to the 100% recommended level of adherence required to achieve
the goal of ART. This is consistent with a recent study of self-reported poor
adherence (< 80%) [8]. With this level of adherence, good CD4 responses were
obtained which may be better with increasing level of adherence.
The
educational status of the participants was not found to be associated with
adherence as their occupational status. This was consistent with the major
reasons reported by the respondents for non-adherence (busy working/at school).
It was very remarkable to observe that pill burden, cost, out of stock of
medicines at the dispensary and lack of understanding of how to take drugs,
etc, were never given as reasons for non-adherence to medications by the
respondents. Despite all these, immunological response was good.
LIMITATIONS
The
researchers were unable to create a control group and hence treatment outcome
for every patient was assessed by comparing the pre-ART CD4-cells counts and
CD4-cells counts while on ART. Fluctuations in absolute CD4 count are known to
occur and hence definite conclusions should be drawn from repeated measurements
[17] but that was not the case with this study. The duration of treatment was
calculated as the time difference between the date of first ART initiation and
the last date of medication refill at the ART pharmacy. Patients’ last date of
medication refill at the pharmacy was used as the date of death. The exact date
of death could not be obtained since almost all death cases took place outside
the hospital setting and was determined through contact tracing and home
visits. The actual causes of the death could also not be ascertained. There
were cases of missing or incomplete records that hampered the study. Some
aspects of data collection were based on self-report, which could be biased.
CONCLUSION
In
this setting, patients receiving ART showed significant improvements in
CD4-cell status and early CD4-cell response but adherence level was relatively
poor. Patients were more stable on zidovudine-based or nevirapine-based
regimens compared to stavudine-based or efavirenz-based regimens. Early
mortality rate was high, indicating a need for early interventions.
CONFLICT OF INTEREST
We
declare no conflicts of interest.
REFERENCES
- Federal Ministry of Health,
FMOH. Technical Report, National HIV/Syphilis Sero-prevalence Sentinel
Survey among Pregnant Women Attending Antenatal Clinics in Nigeria, 2005;
5-7.
- Federal Ministry of Health,
FMOH. Guidelines for the use of Antiretroviral (ARV) drugs in Nigeria. 2005;
pp 25-47.
- Ngwai YB, Odama LE. HIV/AIDS
Prevention Services In: Skill Certification Workshop on HIV/AIDS, STIs,
and Opportunistic Infections for Community Pharmacists, Participant’s
Manual June 2006; 5-6.
- GHAINing Ground. A
Newsletter from Global HIV/AIDS Initiative Nigeria, Family Health
International, 2005; 1 – 4.
- GHAINing Ground. A
Newsletter from Global HIV/AIDS Initiative Nigeria, Family Health
International. 2006; 2 – 5.
- Family Health International.
Update on Global HIV/AIDS initiative Nigeria (GHAIN), Focus on Edo state,
Institute for HIV/AIDS, Arlington, USA. December 2006; 1-4.
- Bolton-Moore C,
Mubiana-Mbewe M, Cantrell RA, Chintu N, Stringer EM, Chi BH. Clinical Outcomes
and CD4-cell Response in Children Receiving Antiretroviral Therapy at Primary
Health Care Facilities in Zambia. JAMA 2007; 298(16): 1888-1899.
- Ferradini L, Jeannin A, Pinoges L, Izopet J, Odhiambo D, Mankhambo L.
Scaling up of highly active antiretroviral therapy in a rural district of
Malawi: an effectiveness assessment, Lancet 2006; 367(9519): 1335 -
1342.
- Corey DM,
Kim HW, Salazar R, Illescas R, Villena J, Gutierrez L, Sanchez J,
Tabet SR. Brief report:
effectiveness of combination antiretroviral therapy on survival and
opportunistic infections in a developing world setting: an observational
cohort study. The Journal of Acquired Immune Deficiency Syndromes, 2007;
44(4): 451-
455.
- Sabin CA (2005). Baseline Characteristics Influence
Benefits from Highly Active Antiretroviral Therapy. AIDS Journal, 2005;
19: pp 1995-2000.
- Osterberg L, Blaschke T. Adherence to medication. N
Engl J Med 2005; 353: 487-497.
- Praska JL, Kripalani S, Seright AL, Jacobsen
TA. Identifying and assisting
low-literacy patients with medication use: a survey of community pharmacies.
Ann Pharmacother. 2005; 39: 1441-1445.
- Vanhove GF, Schapiro JM, Winters MA. Patient
compliance and drug failure in protease inhibitor monotherapy. JAMA 1996;
276: 1955-1956.
- Deeks S, Beatty G, Cohen PT. Viral load and
CD4+ T-cell changes in patients failing potent protease inhibitor therapy.
In: Program and
abstracts of the 5th Conference on Retroviruses and Opportunistic Infections;
February 1-5, 1998; Chicago. Abstract 419.
- Montaner JS, Reiss P, Cooper D. A randomized,
double-blind trial comparing combinations of nevirapine, didanosine, and
zidovudine for HIV-infected patients: the INCAS Trial. Italy, the Netherlands,
Canada, and Australia Study. JAMA 1998; 279: 930-937.
- Melbourne KM., Geletko SM, Brown SL, Willey-Lessne
C, Chase S, Fisher A. Medication
Adherence in Patients with HIV Infection: A Comparison of Two Measurement
Methods AIDS Journal. 1999; Read 9(5): 329 - 338.
- Palella FJ, Deloria-Knoll M, Chmiel JS. Survival
benefit of initiating antiretroviral therapy in HIV-infected persons in different
CD4+ cell strata. Ann Intern Med 2003; 138(8): 620 - 626.
© Pharmacotherapy Group, Faculty of Pharmacy, University
of Benin, Benin City, 300001 Nigeria.
|