Journal of Medical Virology 88:790–797 (2016)
Factors Associated With Poor CD4 and Viral Load
Outcomes in Patients With HIV/AIDS
Imran Ahmed Syed,1,2* Syed Azhar Syed Sulaiman,1 Mohammad Azmi Hassali,1
Shahzad Hasan Syed,3 Lau Hui Shan,2 and Christopher K.C. Lee4
1
School of Pharmaceutical Sciences, Universiti SainsMalaysia (USM), Malaysia
2
School of Pharmacy, International Medical University, Malaysia
3
School of Pharmacy, University of Queensland, Australia
4
Department of Medicine, Hospital Sungai Buloh, Selangor, Malaysia
Suboptimal viral suppression and CD4 response
to antiretroviral treatment (HAART) is known to
cause poor outcomes with the increase cost of
treatment. We aimed to assess factors associ-
ated with such control among HIV/AIDS patients
in Malaysia. Four hundred and six HIV/AIDS
patients, using Antiretroviral Therapy (ART) for
at least the past three months, treated as out-
patients at medication therapy adherence clinics
(MTAC) were recruited. CD4 cell counts, viral
load readings along with co-variants such as
socio-demographic factors, adverse drug reac-
tions, comorbidities, and medication record
were obtained. 1Statistical Package for Social
1
Sciences (SPSS ) version 18 and STATA IC
version 12 were used for data analysis. CD4
counts were found highest among those within
the age category 41–50 years (390.43
272.28),
female (402.64
276.14), other ethnicities
(400.20
278.04), and participants with no for-
mal education (414.87
290.90). Patients experi-
encing adverse effects had a 2.28 (95%CI:1.25–
4.18) fold greater risk of poor CD4 control, while
patients with comorbidities had 2.46 (95%
CI:1.02–5.91) fold greater risk of mild viral sup-
pression. Adverse drug reactions, co-morbid-
ities were found to be significantly associated
with poor immunological and virological out-
comes in HIV/AIDS patients. However, a com-
prehensive evaluation is needed to better
understand other confounders J. Med. Virol.
88:790–797, 2016. # 2015 Wiley Periodicals, Inc.
KEY WORDS: HIV & AIDS; CD4 outcomes;
viral suppression; factors asso-
ciated; anti-retroviral therapy
INTRODUCTION
According to Joint United Nations Program on HIV/
AIDS (UNAIDS) the number of people newly infected

C 2015 WILEY PERIODICALS, INC.
globally is continuing to decline, although the burden
of the epidemic continues to vary considerably between
countries and regions [UNAIDS, 2013]. Ever since HIV
has been recognized; reduction in viral load with an
increase in CD4 cell counts remained as prime objec-
tives of antiretroviral treatment along with enhance-
ment in health related quality of life with a reduction
in the impact of HIV transmission in the community.
No matter how we define, the principal goal of HIV
treatment is to prevent or reverse the progression of
clinical illness [Goldschmidt and Dong, 2000].
There is no doubt that the unprecedented increase
in access to HIV treatment even in the resource-
limited settings has definitely contributed towards
the global improvement in the epidemics and HIV/
AIDS related morbidity and mortality. This made
possible due to virological suppression that occurs in
approximately 70% of patients during the first regi-
men of HAART [Hunt et al., 2003] [3], and thus
making the immunologic reconstitution possible [May
et al., 2007; Thompson et al., 2010]. Many factors
contribute to immunological enhancements and viro-
logical suppression in making Highly Active Antire-
troviral Treatment (HAART) as an effective tool
[Eldred and Malitz, 2007] against HIV and AIDS and
it was found that patients who present with advanced
HIV infection and high levels of viral replication
continue to be a challenge in the HAART era [Town-
send et al., 2009; Casotti et al., 2011]. This becomes
an important point of concern as a substantial
number of patients start their first-line antiretroviral
therapy at an advanced stage of an HIV-1 infection
[van Leth et al., 2005].

Correspondence to: Syed Imran Ahmed, Department of
Pharmacy Practice, School of Pharmacy, International Medical
University (IMU), Kuala Lumpur, Malaysia.
E-mail: sia194@yahoo.com
Accepted 21 September 2015
DOI 10.1002/jmv.24389
Published online 5 October 2015 in Wiley Online Library
(wileyonlinelibrary.com).
Factors Affecting Poor CD4 and Viral load outcomes 791

It has been suggested that a lower pre-HAART Measurement of Outcome–CD4 and Viral Load
CD4 count nadir may lead to a greater risk of Counts
experiencing HAART related toxicity, in addition the
We used 500 cells/mL or less as the cut-off point to
frequency of a paradoxical immunologic response to
define optimal immunological control, similarly >75
HAART, defined as viral suppression without CD4
copies/ml was used as the cut-off to determine
cell-count improvement, has also been reported in the
optimal viral load control; which is according to the
literature as 8–42%, around 15% in most instances
standards of practice in HIV care [Panel on Antire-
[Colette et al., 2005; Casotti et al., 2011].
troviral Guidelines for Adults and Adolescents, 2015].
In Malaysia it was estimated that about 86,000
Means of five most recent CD4 and viral load counts
patients were living with status of HIV and AIDS
readings were calculated. The mean values with 95%
with an estimation of 38,420 eligible for HIV treat-
confidence interval were then used for all compar-
ment by the end of 2013. The epidemic in this
isons. The monitoring of CD4 and viral load counts
country is still concentrated within most-at-risk pop-
are considered the gold standard for HIV/AIDS
ulations (MARPS) especially among IDU, sex work-
patients. For regression, the variables, CD4 counts
ers, and transgender population [MOH, 2014].
and viral load were also used as categorical variables.
Although significant progress has been made in the
We categorized CD4 counts into: normal CD4 counts
country’s response to HIV/AIDS, scaling up preven-
(>500 cells/mL), moderate CD4 counts (200–500 cells/
tion, treatment, and care to meet Universal Access
mL), and poor CD4 counts (<200 cells/mL). For viral
goals remain a challenge in this country [Barmania,
load counts, we classified the continuous viral load
2013]. Given the fact that assessing factors affecting
counts into four categories based on quartile ranges:
poor immunological and virological outcomes are
(1) optimal viral suppression, (2) moderate viral
essential in planning HIV/AIDS treatment, we aimed
suppression, (3) mild viral suppression, and (4) poor
to determine the association of such factors (whether
viral suppression.
or not they are statistically significant) among a
cohort of HIV/AIDS patient in Malaysia.
Measurement of Co-Variates
MATERIALS AND METHODS Potential confounders and risk factors were identi-
fied on the basis of their association with outcomes and
Four hundred and forty three Malaysians with
a priori knowledge. Socio-demographic information
known diagnosis of HIV/AIDS, who were using Anti-
including age, ethnicity, education, occupation, and
retroviral Therapy (ART) for at least past three
monthly income were collected from the participants.
months, and treated as outpatients at medication
Clinical parameters such as co-morbidities or medical
therapy adherence clinics (MTAC) at Hospital Sungai
conditions other than HIV, adverse effects, and medi-
Buloh, were invited to participate in this study
cation were obtained from participants’ medical re-
(July–October 2012). Hospital Sungai Buloh is the
cords. Data on adverse drug reactions were collected
largest infectious disease referral centre in the coun-
through a self-administered questionnaire, where par-
try. The study was conducted according to the
ticipants were asked “Have you EVER experienced
principles expressed in the Declaration of Helsinki,
adverse effects after taking your HIV medications
and was approved by the Medical Research & Ethics
(anti-retroviral therapy)?” with response options “yes”
Committee (MREC) and Clinical Research centre
or “no.” Subjects were categorized as having adverse
(CRC), Ministry of Health Malaysia. The study was
drug reactions if they answered “yes” to this question.
also registered with the National Medical Research
This information was further confirmed by patients’
Registry (NMRR).
medical records, while the information about the
Patients were categorized as having HIV if they
antiretroviral therapy and individual drugs were also
were attending MTAC for the management of HIV,
collected from patients’ medical records.
and every second patient with HIV on the respective
patients’ list at the clinic sites was recruited. Prior to
Statistical Analysis
information gathering a study information sheet was
provided and verbal or oral consents were taken. The data were analysed using the1
Statistical Pack-
Other relevant clinical information, including details age for Social
1
Sciences (SPSS ) version 20 and
of medications, viral load and CD4 cell counts were STATA IC version 12, with a significance level of
also obtained from patients’ medical records. 0.05. Descriptive statistics were used to calculate
Face-to-face interviews were conducted at the out- percentages frequencies, means, and standard devia-
patient clinics, using a questionnaire which had been tions. The relationship between variables for catego-
subjected to content and face validation and reviewed rical data was performed using the X2 (Chi-Sq).
by individuals who were not experts in the design and Comparisons between groups with normal distribu-
testing of the instrument. The validated English version tion were performed using the Student’s t-test and
of the questionnaire had been translated into the Malay One-way ANOVA. Pearson’s correlation test was used
language (Bahasa Malaysia) with forward/backward to verify the existence of a correlation between mean
translation, and piloted on a sample of 30 participants. scores or other values.
J. Med. Virol. DOI 10.1002/jmv
792 Syed et al.

We presented our results in the form of crude odds TABLE I. Socio-Demographics of the Study Population
ratios (ORs) to establish the association between CD4 (N ¼ 406)
counts and viral load and factors. The crude odds Variables N %
ratio is an unadjusted measure of the association in
the aggregate form and it does not control for Age
18–30 47 11.58
possible confounding. Therefore, a series of multiple 31–40 174 42.86
logistic and multinomial regression models (see foot- 41–50 122 30.05
notes of Tables III and IV) were used to determine >50 63 15.52
the association of CD4 and viral load counts and Gender
socio-demographic and clinical factors assessed as Male 292 71.92
Female 114 28.08
categorical outcomes. The effects were adjusted for Ethnicity
age, gender, ethnicity, education, marital status, Malay 122 30.05
comorbidity, and type of HIV treatment. For potential Chinese 205 50.49
confounding, the unadjusted associations were com- Indian 33 8.13
Others 46 11.33
pared with the adjusted associations, with confound- Marital status
ing confirmed when the unadjusted effect size and Married 200 49.26
adjusted effect size estimates differed. Unmarried 166 40.89
Divorced 34 8.37
RESULTS Widowed 6 1.48
Education level
The study generated data from a total of 406 No formal education 53 13.05
respondents participated. Out of which 72% (n ¼ 292) Primary education 89 21.92
Secondary education 207 50.99
were male with 42.86% (n ¼ 174) from age group Graduate 46 11.33
between 31 and 45 years. Almost 50% of respondents Postgraduate 11 2.71
were Chinese, while secondary school education level Occupation
was found to be highest (50.99%) education level, Unemployment 107 26.35
Labor 171 42.12
with 50.0% working adults (Table I). Professional 24 5.91
Housewife 32 7.88
Factors Associated With CD4 Counts Retired 13 3.20
Others 59 14.53
In terms of socio-demographics of the study popula- Co morbidities
tion, CD4 counts were highest among those within No 358 88.18
the age category 41–50 years (390.43
272.28), fe- Yes 48 11.82
Adverse effects
male (402.64
276.14), other ethnicities No 233 57.39
(400.20
278.04), and participants with no formal Yes 173 42.61
education (414.87
290.90). In case of clinical factors, Type of HIV treatment
participants without comorbidities (377.58
257.69), Other dugs therapy 186 45.81
reported adverse effects (398.62
254.92) and receiv- Combivir based therapy 220 54.19
ing combivir based therapy (377.80
223.78).
Although there were noticeable differences between
the factors, none of the factors were associated with
CD4 counts were not significantly associated with
CD4 counts of more than 500 cells/mL (normal CD4
any of the included factors.
counts).
The large groups of participants aged 31–40 years,
Factors Associated With Viral Load Counts
male, Chinese, no comorbidities and adverse effects,
and participants on combinations therapy have small Table II depicts the means and 95% confidence
standard errors, while the smallest groups have the intervals of socio-demographics, and clinical factors
largest. Correspondingly, the confidence interval is that may affect the viral load counts of the partic-
widest for these latter categories (Table II). We might ipants. Viral load counts were noted highest in terms
also notice that all confidence intervals are over- of gender and ethnicity, in which viral load counts
lapping. Significant differences are noticed between were lowest among male patients (9050.9
46254.1,
no adverse effects and adverse effects (difference Pr ¼ 0.026) and those with Chinese origin
57.4cells/mL, Pr ¼ 0.021). (8544.4
43367.1, Pr ¼ 0.009). Like CD4 counts, the
In the case of quartile-based categories (derived large groups of participants have small standard
from a continuous CD4 counts), only adverse effects errors, while the smallest groups have the largest.
were a strong predictor of poor CD4 counts Correspondingly, the confidence interval is widest for
(Table III). The associations remained consistent and these latter categories. We might also notice that all
robust after adjustment for potential confounders. In confidence intervals are overlapping.
the fully adjusted model, patients experiencing ad- In the case of quartile-based categories, none of the
verse effects had a 2.28 (95%CI:1.25–4.18) fold factors was significantly associated with poor viral
greater risk of poor CD4 control, while, moderate suppression. Only the presence of comorbidities
J. Med. Virol. DOI 10.1002/jmv
 TABLE II. Means and Standard Deviations of CD4 and Viral Load Counts, by Socio-Demographics

CD4 counts (cells/mL) Viral load (copies/ml)

Variables N Mean SE 95%CI P-value N Mean SE 95%CI P-value

Age
18–30 47 380.8 33.4 313.6–448.1 0.758 43 18119.5 12693.9 7497.9–43736.9 0.769
31–40 174 359.5 18.7 322.7–396.3 150 14694.1 4998.2 4817.7–24570.5
41–50 122 390.4 24.7 341.6–439.2 113 39524.5 31320.3 22532.6–101581.6
>50 63 378.2 28.0 322.2–434.3 59 19985.3 10106.8 245.7–40216.3
Gender
Male 292 363.0 13.8 335.8–390.3 0.074 257 9050.9 2885.3 3369.1–14732.8 0.026
Factors Affecting Poor CD4 and Viral load outcomes

Female 114 402.6 25.7 351.4–453.9 108 58357.0 33442.1 7938.1–124652.2

Ethnicity
Malay 122 351.3 19.7 312.3–390.2 0.596 112 21272.1 6686.1 8023.1–34521.1 0.009
Chinese 205 378.1 18.7 341.3–414.9 187 8544.4 3171.3 2288.0–14800.8
Indian 33 397.9 48.4 299.3–496.5 30 136048.7 117773.1 104824.2–376921.7
Others 46 400.2 32.0 335.7–464.7 36 15747.6 14339.1 13362.3–44857.6
Co morbidities
No 358 377.6 13.6 350.8–404.4 0.775 318 26996.3 11626.8 4120.9–49871.8 0.389
Yes 48 348.7 23.5 301.3–396.1 47 932.4 837.3 752.9–2617.8
Adverse effects
No 233 398.6 16.7 365.7–431.5 0.021 215 10754.7 3441.4 3971.3–17538.1 0.128
Yes 173 341.2 17.9 305.8–376.7 150 42109.3 24140.5 5592.6–89811.2
Type of HIV treatment
Other drugs therapy 186 369.8 20.2 330.0–409.7 0.748 162 35635.7 22039.2 7887.4–79158.8 0.291
Combivir based therapy 220 377.8 15.1 348.1–407.5 203 14067.4 4802.9 4597.0–23537.7

One-way Anova for age and race; t-test for the rest.
793

J. Med. Virol. DOI 10.1002/jmv

794 Syed et al.
TABLE III. Association of Socio-Demographics and Clinical Factors With CD4 Counts

Moderate CD4 counts

200–500 cells/mL Poor CD4 counts <200 cells/mL

Normal >500 cells/mL Unadjusted OR Adjusted OR Unadjusted OR Adjusted OR

Factors Referent (95%CI) (95%CI) (95%CI) (95%CI)
Age
18–30 1.0 1.0 1.0 1.0 1.0
31–40 1.0 0.92 (0.40–2.09) 1.11 (0.47–2.58) 1.55 (0.58–4.22) 1.63 (0.58–4.61)
41–50 1.0 0.69 (0.30–1.60) 0.76 (0.31–1.83) 1.11 (0.40–3.11) 0.97 (0.33–2.87)
>50 1.0 0.58 (0.23–1.46) 0.66 (0.24–1.77) 0.58 (0.23–1.46) 1.02 (0.31–3.41)
Gender
Male 1.0 1.0 1.0 1.0 1.0
Female 1.0 0.67 (0.39–1.13) 0.82 (0.45–1.48) 0.74 (0.40–1.35) 0.81 (0.41–1.60)
Ethnicity
Malay 1.0 1.0 1.0 1.0 1.0
Chinese 1.0 1.07 (0.60–1.89) 1.03 (0.56–1.89) 0.92 (0.48–1.73) 0.94 (0.48–1.84)
Indian 1.0 0.78 (0.32–1.92) 0.91 (0.35–2.37) 0.45 (0.15–1.39) 0.43 (0.13–1.39)
Others 1.0 0.99 (0.44–2.26) 0.88 (0.36–2.15) 0.50 (0.18–1.39) 0.45 (0.15–1.36)
Type of treatment
Other drugs 1.0 1.0 1.0 1.0 1.0
therapy
Combivir based 1.0 1.09 (0.67–1.78) 1.06 (0.64–1.77) 0.71 (0.40–1.24) 0.66 (0.36–1.17)
therapy
Adverse effects
No 1.0 1.0 1.0 1.0 1.0
Yes 1.0 1.34 (0.81–2.22) 1.49 (0.87–2.54) 1.88 (1.06–3.33) 2.28 (1.25–4.18)
Co morbidities
No 1.0 1.0 1.0 1.0 1.0
Yes 1.0 1.23 (0.59–2.58) 1.17 (0.54–2.51) 0.62 (0.24–1.62) 0.55 (0.21–1.48)

ORs were adjusted for age, gender, ethnicity, education, marital status, comorbidity, adverse effects and type of HIV treatment.
Multinomial regression.

significantly associated with mild viral suppression.
The associations remained consistent and robust
after adjustment for potential confounders. In the
fully adjusted model, patients having comorbidities
had a 2.46 (95%CI:1.02–5.91) fold greater risk of mild
viral suppression (Table IV).
DISCUSSION
There is no uncertainty about the effectiveness of
CD4 and viral load monitoring as part of disease
prognosis in the management of HIV, therefore the
present study aimed to find factors associated with
poor immunological and virological outcomes among
Malaysian patients. We also believe that so far no
literature available pertaining to this in the country;
hence it will be serving as a baseline data for future
researches in the similar context.
The study found highest levels of CD4 cell counts
with age 41–50 years, females, patient belonged to
other ethnicities (other than three main Malaysian
ethnic groups), those reported adverse drug reactions,
on multiple drug therapy and having no comorbidities;
though there were no significant associations found.
Significant differences were noticed with respect to
adverse drug effects, where patients experiencing
adverse effects were having a high likely hood of poor
CD4 control. It is widely known that many factors,
including late diagnosis, insufficient antiretroviral use,
J. Med. Virol. DOI 10.1002/jmv
poor patient compliance, drug toxicities, drug resist-
ance or intolerance could contribute towards a poor
CD4 outcome which pose significant barriers in achiev-
ing optimal treatment outcomes [Eldred and Malitz,
2007; Glass et al., 2012]. In addition a suboptimal CD4
T-cell responses to antiretroviral therapy (ART) have
been found associated with substantial increases in the
risk of AIDS-related and non-AIDS-related mortality
and morbidity, including cardiovascular disease, liver
disease, renal disease, and malignancies [El-Sadr
et al., 2006; Moore et al., 2006; Baker et al., 2008; van
Lelyveld et al., 2012]. It is also important to note that,
AIDS-defining events are rare in virally suppressed
HIV patients, even among those with low CD4 cell
counts; however, inadequate CD4 response to success-
ful ARTs is associated with increased risk of non-
AIDS-related morbidity and mortality [Helleberg
et al., 2013].
Alongside the CD4 monitoring, viral load is the
most important indicator of initial and sustained
response to ARTs and should be measured in all
HIV-infected patients at entry into care, at initiation
of therapy, and on a regular basis thereafter [Panel
on Antiretroviral Guidelines for Adults and Adoles-
cents, 2015], and the goal is to have a viral load
undetectable. Although viral suppression is defined
as a level below the lower limits of detection depend-
ing upon the assay used [Kieffer et al., 2004], optimal
viral suppression is generally defined as a viral load
Factors Affecting Poor CD4 and Viral load outcomes 795
TABLE IV. Association of Socio-Demographics and Clinical Factors With Viral Suppression, Using Quartile-Based
Categories

Moderate suppression Mild suppression Poor suppression

Optimal
Suppression Unadjusted Adjusted Unadjusted Adjusted Unadjusted Adjusted
Factors Referent OR (95%CI) OR (95%CI) OR (95%CI) OR (95%CI) OR (95%CI) OR (95%CI)
Age
18–30 1.0 1.0 1.0 1.0 1.0 1.0 1.0
31–40 1.0 0.94 0.94 0.92 0.89 1.12 1.05
(0.37–2.37) (0.35–2.50) (0.34–2.47) (0.32–2.52) (0.44–2.81) (0.39–2.40)
41–50 1.0 1.41 1.44 1.50 1.32 1.36 1.29
(0.53–3.74) (0.50–4.13) (0.54–4.18) (0.44–3.97) (0.51–3.63) (0.44–3.77)
>50 1.0 0.89 0.76 2.18 1.77 2.08 1.21
(0.27–2.97) (0.21–2.80) (0.69–6.85) (0.51–6.12) (0.70–6.23) (0.36–4.10)
Gender
Male 1.0 1.0 1.0 1.0 1.0 1.0 1.0
Female 1.0 1.43 1.17 0.91 0.75 1.43 1.29
(0.75–2.75) (0.56–2.46) (0.46-1.82) (0.34-1.66) (0.77–2.68) (0.63–2.65)
Ethnicity
Malay 1.0 1.0 1.0 1.0 1.0 1.0 1.0
Chinese 1.0 1.41 1.28 1.26 1.30 0.71 0.57
(0.71–2.81) (0.61–2.69) (0.64–2.49) (0.62–2.75) (0.38–1.34) (0.28–1.14)
Indian 1.0 1.66 1.47 1.76 1.82 1.64 1.26
(0.44–6.16) (0.37–5.77) (0.49–6.29) (0.48–6.92) (0.51–5.22) (0.37–4.36)
Others 1.0 2.07 1.77 0.95 0.96 0.93 0.69
(0.72–5.96) (0.56–5.55) (0.59–3.11) (0.27–3.46) (0.33–2.65) (0.22–2.20)
Type of treatment
Other drugs 1.0 1.0 1.0 1.0 1.0 1.0 1.0
therapy
Combivir 1.0 0.69 0.72 0.55 0.55 0.93 0.95
based (0.38–1.26) (0.38–1.34) (0.30–1.01) (0.29–1.05) (0.52–1.65) (0.51–1.77)
therapy
Adverse effects
No 1.0 1.0 1.0 1.0 1.0 1.0 1.0
Yes 1.0 1.20 1.13 0.96 0.85 1.31 1.40
(0.66–2.19) (0.59–2.16) (0.52–1.79) (0.43–1.65) (0.74–2.33) (0.75–2.61)
Co morbidities
No 1.0 1.0 1.0 1.0 1.0 1.0 1.0
Yes 1.0 1.03 1.07 2.35 2.46 0.65 0.66
(0.41–2.60) (0.41–2.82) (1.02–5.40) (1.02–5.91) (0.25–1.73) (0.23–1.85)

ORs were adjusted for age, gender, ethnicity, education, marital status, comorbidity, and type of HIV treatment. Multinomial regression.

persistently below the level of detection (HIV RNA
<20–75 copies/mL); whereas a virological failure is
often referred to >200 copies/mL [Panel on Antiretro-
viral Guidelines for Adults and Adolescents, 2015].
However the data on the association between persis-
tently low level but quantifiable viremia (HIV RNA
<200 copies/mL) and virological failure is conflicting
[Panel on Antiretroviral Guidelines for Adults and
Adolescents, 2015]. Interestingly, we found that fe-
male patients were having significantly poor viral
load suppression in comparison to their male counter-
parts, suggesting a better virological outcome in male
HIV patients, which appeared to be consistent with a
regional study in Vietnam where trend towards
increased viremia was observed among women on
ARTs that warrants further investigation [Trinh
et al., 2011]. These outcomes highlights the need for
further investigations since both findings were from
the South East Asian region. A recent study did not
find any significant role of genetic variants in the
sustained viral suppression and concluded that the
risk of virological failure decreased with longer
duration of viral suppression [Glass et al., 2012].
However, even after adjusting variations in prior
ART exposures and the possibility of resistance, the
potential impact of genetic variations cannot be
excluded [Glass et al., 2012].
In our study hypertension (11%), hyperlipidaemia
(10.4%), and diabetes mellitus (8.3%) were found three
most common co-morbid conditions among HIV patients
and it was found that patients with co-morbidities had
higher risk of mild viral load suppression, which also
indicate a number of factors contributing for such
responses. Comorbidities and concomitant illnesses are
known to cause poor CD4 response and viral suppres-
sion [Eshun-Wilson et al., 2012; Zanoni et al., 2012].
Achieving and maintaining viral suppression requires
stringent adherence to treatment, failure to do so
encourages selection of resistant viral strains which
have implications for both personal and public health.
Therefore adherence education, ongoing support, and
treatment components and dosing to fit lifestyle are
J. Med. Virol. DOI 10.1002/jmv
796
critically important issues [Thaker 2003]. We may not
be able to produce specific reasons for such finding but
studies have indicated various reasons for lower sus-
tained viral suppression among specific populations and
irrespective of the reason and population it affects, such
suboptimal viral suppression may lead to worse clinical
outcomes and increased costs [Yehia et al., 2012].
We understand the deep-rooted phenomenon of
paradoxical immunologic response (PIR) to Highly
Active Antiretroviral Therapy (HAART), defined as
viral suppression without CD4 cell-count improve-
ment has been reported in the literature as 8–42%,
around 15% in most instances [Casotti et al.,
2011] and we did not attempt to find this in our
study. As the data is missing in the local setting we
hope to provide common factors resulting in poor
immunological and virological outcomes, so that
appropriate measures should be taken in practice to
optimise the use of antiretrovirals and further re-
searches can be tailored. Unfortunately, even though
several approaches have been suggested and inves-
tigated, no consensus has been reached yet on the
most efficacious treatment for immunological non-
response. Thus, we are now facing a dichotomy,
whereby the ever-growing list of new-class antiretro-
virals provides us with the most potent weapons
against HIV/AIDS, while we still lack a full grasp on
the most proper means of administering them. How-
ever, even though such research has not yet provided
a unique treatment protocol, research has revealed
diverse immune-virological and even genetic patterns
behind impaired CD4þ T cell count recovery [Egger
et al., 2009; Gazzola et al., 2009].
CONCLUSION
Adverse drug reactions and co-morbidities appeared
to have significant associations with poor CD4 recovery
and viral suppression. Based on the findings and other
available data appropriate measures must be taken to
rectify the challenges in achieving goals of HIV/AIDS
treatment, many of these issues are linked to poor
adherence & follow up, lack of awareness and counsel-
ling about side effects etc. It has been shown that such
interventions has resulted in higher virological sup-
pression in patients with severe follow-up and adher-
ence barriers [Elıas Casado et al., 2012].
STRENGTHS AND LIMITATIONS
The novelty of the findings in the local context is one
of the strengths of the present study, which shall provide
the basis for further investigations. However, the cross-
sectional design, lack of data regarding initiation of
ARTs by individual patients, could limit its implication.
FUTURE DIRECTIONS
More longitudinal researches are needed to help
better understand these factors and associated issues.
Such investigations should be tailored to patients
J. Med. Virol. DOI 10.1002/jmv
Syed et al.
with adverse drug reactions, comorbidities, advance
HIV infection, poor adherence and follow up etc. It is
imperative to have such localized data in order to
optimise the outcomes of HIV program. This key area
of HIV research requires ongoing investigation and
warrants the design of studies explicitly aimed at
examining the mechanisms underlying immunologic
nonresponse. One major limitation of such research
has been a lack of uniformity in the definition of
“immunologic non-responder” [Okulicz 2012].
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