Navin AP et al: Evaluation of Antiretroviral Therapy

Original article

Evaluation of the effects of anti-retroviral drug regimen

(Stavudine + Lamivudine + Nevirapine) on CD4 count,
body weight, and haemoglobin of HIV positive patients: A
retrospective study
Reshma S R, Navin A P*, Narendranath S, Dinakar K R, Keerthi Sagar J, Somashekar H S, Vaneet
Aggarwal
Email: navin903@gmail.com

Abstract
Human immunodeficiency virus infection (HIV) has become a manageable disease due to antiretroviral therapy.
Although many treatment schedules are effective in controlling the viral load, maintaining it for a long period
is difficult due to many factors such as adverse effects, long-term toxicity, and dosing schedules, all of them
may result in poor patient compliance, treatment failure and drug resistance. The evaluation of these treatment
schedules in terms of their efficacy, duration, and acceptance is an important aspect for treating doctors, patients,
and policy makers. Therefore, our objective is to evaluate stavudine, lamivudine, and nevirapine regimen in the
management of HIV infection in our hospital. Methodology: An observational study was done in the ART
centre of CG Hospital, Davanagere. The data were collected for the duration of 12 months (June 2012 to May
2013). Institutional ethics committee approval was taken before the initiation of the study. For inclusion in the
study, the patients had to be antiretroviral (ARV) naive and receiving their ARV medication i.e., a combination of
stavudine, lamivudine, and nevirapine therapy through the Government ART Program. Results: Among the 94
patients included, CD4 count after 6 months of treatment was 303 cells/mm3 as compared to the initial count of
163 cells/mm3. Likewise, an improvement was recorded in hemoglobin level and body weight by approximately
2g% and 3 kg, respectively. Conclusion: In the present study, there was a significant improvement in CD4 count,
body weight, and haemoglobin level when compared to the initial, after 6 months of treatment with combination
therapy of stavudine, lamivudine and nevirapine. However, there was no difference in response between the
severe ill patients (CD4 count < 200 cells/mm3) when compared to the patients with CD4 count ≥ 200 cells/
mm3. HIV infection can be tackled by a combined approach of multidrug therapy to prevent resistance and
community based approach with good nutritional and dietary supplementation.

Key words: ART Regimen, CD4 Counts, Body Weight, Anaemia

Introduction improved the mortality, morbidity, and the quality

The human immunodeficiency virus (HIV) of life among the HIV infected patients.2
infection has become a manageable disease due According to WHO estimate 1.1 million Asians
to antiretroviral therapy (ART).1 Three drugs are currently in need of the ART, but only
are used in order to reduce the likelihood of the 6%–7% having access to it3. No doubt that the
virus developing resistance. The ART has greatly antiretroviral treatment has reduced AIDS- related
Navin A P1 , Somashekar H S2, Reshma S R3, Dinakar K R3 Department of Pharmacology,
3
JJM Medical College,
Narendranath S3, Keerthi Sagar J3, Vaneet Aggarwal3 Davanagere, Karnataka
1
Assistant Professor, Department of Pharmacology, Kasturba
Medical College, Manipal University, Manipal-576104 *Corresponding Author
2
Department of Pharmacology, Vishwabharathi Medical College
and General Hospital, Kurnool.

How to cite this article: Reshma SR, Navin AP, Narendranath S, et al. Evaluation of the effects of antiretroviral drug regimen (Stavudine
+Lamivudine + Nevirapine) on CD4 count, body weight, and haemoglobin of HIV positive patients: A retrospective study. MJMS. 2016; 1(2): 37-41.

Manipal Journal of Medical Sciences | December 2016 | Volume 1 | Issue 2 37

 Navin AP et al: Evaluation of Antiretroviral Therapy
death. Approach to therapy is not universal, and
the possibility of curative therapy and a successful
vaccine are indeterminate.4
The implementation of the ART regimen has been
plagued by certain serious pitfalls, amongst which
the exorbitantly high costs, weak infrastructure, an
utter lack of specialized care and human resources
figure prominently.
Despite being a multitude of ART regimens
with ability of lowering plasma viral loads below
detectable limits, optimization of their durability,
safety and ease of administration have hampered
their implementation. Further, the toxicity seen
with protease inhibitors (PI) use has propelled
non-nucleoside reverse transcriptase inhibitors
(NNRTIs) into the frontline as a part of the initial
regimen.1
Nevirapine (NVP) in combination with stavudine
(d4T) and lamivudine (3TC) has emerged as the
most popular choice of the first line ART, in both the
developed and the under-developed regions. Hence,
this warrants that all the stakeholders so involved be
aware of its anti-retroviral efficacy, durability, and
safety profile.5
Therefore, our objective is to evaluate the combination
of stavudine, lamivudine, and nevirapine in the
treatment of HIV infection in our hospital.
Objectives
1. To evaluate the efficacy of the combination of
Stavudine, Lamivudine, and Nevirapine of ART
regimen in the treatment of HIV infection in
our hospital.
2. To check the magnitude of response in severely
ill patients and non-severely ill patients.
Materials and Methods
Study Design: This was a retrospective study.
The study site was ART centre of CG Hospital,
Davanagere. The data was collected for the duration
of 12 months (June 2012 to May 2013). Ethics
committee approval was taken before initiation of
the study. Permission was also obtained from the
officer in charge of the ART centre to access the
records. Prescriptions of the patients were collected
38 Manipal Journal of Medical Sciences | December 2016 | Volume 1 | Issue 2
and the relevant information was entered in the
preformed proforma and analysed.
Study Population: Patients belonging to different
age groups, visiting the HIV clinic between the
periods from 1 January 2010 to 30 September
2012 were included in our study. Only the patients
who were either the ART naïve or receiving
the combination of stavudine, lamivudine, and
nevirapine (SLN) through the government ART
program were included in our study. Further, in the
case of the patients on SLN regimen, only those
subjects who were compliant for a period of six
months were included in our study. Exclusion criteria
involved unreliable data on baseline characteristics
and ART history as well as initiation of a second
ART regimen on admission and unavailability of
baseline CD4 values.
Study Setting: Outpatient at ART centre of CG
Hospital, a tertiary care centre in Davanagere.
Sample Size: During the period of 12 months (June
2012 to May 2013), 94 case sheets of the patients
diagnosed to have HIV infection and meeting the
inclusion criteria were studied.
Informed Consent: Informed consent of the
patients was not taken (as it was a retrospective
study) and the data obtained was kept confidential.
Statistical methods
In this study, the data was analysed using Descriptive
Statistics. Analysis to check for the changes after 6
months of the treatment in the parameters such as
CD4 counts, haemoglobin, and body weight was
carried out. Wilcoxon matched pairs signed rank
test was applied to compare the CD4 counts. Paired
t test was applied to compare the weight and the
haemoglobin levels before the treatment and after 6
months of treatment. An unpaired t test was applied
between the groups to check for the response.
Results
Demographic Profile of the Study Population:
The Demographic characteristics of the patients are
shown in Table 1. In this study, 94 case records were
evaluated. Out of these 16 cases belong to paediatric
age group (≤ 14 years) of which 9 were males and 7
 Navin AP et al: Evaluation of Antiretroviral Therapy

females. Remaining 78 cases were of the age group Median baseline parameters with interquartile
between 15 and 65 years of which 18 were males range (IQR) of efficacy parameter, the CD4 count
and 60 females. is 162.5 (82.25 – 270) cells/mm3 when compared to
Table 1: Demographic characteristics of HIV infected individuals 6 months after the treatment 303 (197 – 455) cells/
receiving the combination therapy – stavudine, lamivudine, and mm3 that was statistically significant with the p
nevirapine (SLN)
value of < 0.0001.
Age group Total Males Females
< 14 years 16 9 7 Another efficacy parameter assessed was the
15-65 years 78 18 60 bodyweight and its median and IQR after the
treatment was 45 (37 -52) kg compared to 42 (32.75
Table 2: CDC classification of HIV infected individuals based on
their baseline CD4 counts – 50) kg at the baseline which was statistically
CD4 counts Total Males Females significant (p < 0.0001).
(cells/mm3)
The Hb percentage which we have considered as
>500 4 2 2
the efficacy parameter showed significant increase
200-499 34 8 26
i.e., median and IQR 11.18 (9.8 – 12.12) g% after 6
<200 54 16 38
months of treatment when compared to the baseline
Table 3: A comparison of different parameters measured in the value 9.35 (8.11 – 11.18) g% which was statistically
study for the assessment of efficacy in the combination therapy
– stavudine, lamivudine, and nevirapine (SLN); P values obtained significant (p < 0.0001).
from paired t-test
Parameters Baseline After p value
Both the groups were compared based on the three
treatment parameters – CD4 count, bodyweight, and Hb level.
CD4 Counts 162.5 ( 82.25- 270) 303(197 - 455) <0.0001 There was no significant difference between the
(cells/mm3) two groups in response to the treatment that is in
Hb levels (g %) 9.35 (8.1 - 11.18) 11.18 (9.8 - <0.0001 patients with CD4 counts < 200 cells/mm3 and ≥
12.15)
200 cells/mm3. By this, we can say that the severely
Body 42 (32.75 - 50) 45.00 (37 - 52) <0.0001
Weight (kg) ill patients respond equally to the treatment regimen
with the combination of stavudine, lamivudine, and
Table 4: A comparison of different efficacy parameters between
the severe and the non-severe cases receiving SLN therapy (All nevirapine.
values as median and interquartile ranges)
Parameters Group A (CD4 Count Group B (CD4 Count ≥
Discussion
<200 cells/mm3) 200 cells/mm3) The present study was intended to evaluate the
Baseline After Baseline After efficacy of the combination stavudine, lamivudine,
treatment treatment
and nevirapine in the community without the
CD4 counts 98 221.5 (157 293 428 (326
(cells/mm3) (50.5- 42.3) - 315.5) (248.3- 350.8) - 604)
consideration of coexisting illnesses. A multitude
of reasons, including enhanced potency of drugs,
Hb levels (g %) 9.2 (7.8 11.20 10.2 (8.3 11.1 (10.1
- 11.03) (9.6- 12.20) - 11.2) - 12.38) better tolerability, and compliance have ensured a
Body Weight 40 (32.75 45 (37 46 (40 - 50.5) 46.5 (40.75 greater viral suppression rates with the existing
(kg) - 50) - 51.75) - 54.25) ART regimens in comparison to the other host
of initial multi-drug therapies. In clinical trials,
In the present study, we divided the patients into 2
groups based on the baseline CD4 counts < 200 cells/ 70% of the patients recorded sustained periods
mm3 as group A and ≥ 200 cells/mm3 as group B. of viral suppression with the ART regimens. The
efficacy parameter considered for the analyses
The efficacy parameters in our present study are was CD4 counts, which is one of the important
the response to treatment which can be evaluated parameters utilized for monitoring the patient on
by knowing the increase in the CD4 counts when ART treatment. Along with this, the hemoglobin
compared to the baseline, the improvement in the level and the bodyweight were considered for the
Hb percentage, and the bodyweight. evaluation of efficacy. In our study, we have observed

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 Navin AP et al: Evaluation of Antiretroviral Therapy
an improvement in the CD4 counts after 6 months
of ART therapy with increase in hemoglobin level.
There was also increase in the body weight in the
treatment group.
A study revealed that the SLN regimen is associated
with the increased durability of anti-retroviral
activity and better immunological response in
patients with advanced HIV infections. A switch to
another drug can mitigate the concerns with the
long-term safety of stavudine by an appropriate time.
However, this strategy needs a further evaluation.6
Another study done by Desakorn V et. al., showed
that the SLN regimen had increased the CD4
cell count and the bodyweight with reduction in
opportunistic infections. Thus, they concluded
that the SLN regimen had both clinical and
immunological benefits but one third of the patients
had adverse effects.7
One more study by Getahun A showed that the SLN
was well tolerated and effective in increasing the
CD4 counts and suppressing plasma viremia in the
advanced HIV infections during the 48-week follow-
up periods.8
A Nigerian study revealed that the SLN regimen
had produced excellent viral suppression, enhanced
immunological response, and a relatively better
quality of life for the patients over the 12-month
treatment period.9
The efficacy of SLN regimen received a shot in
the arm from the results of a study conducted in
the United States of America, which showed that
the SLN remained effective irrespective of prior
treatment or baseline viral loads.10
An optimal virucidal efficacy, durability of its anti-
retroviral action, easy tolerability, least possibility of
adverse effects with minimal drug-drug interactions
are the hallmarks of an ideal initial ART regimen.
In regions with recorded ZDV resistance, d4T can
be used instead. Some of the commonly observed
adverse effects include peripheral neuropathy, lipo-
atrophy, steatohepatitis and hyperlactaemia. 3TC
use is associated with a host of adverse effects like
40 Manipal Journal of Medical Sciences | December 2016 | Volume 1 | Issue 2
anaemia, gastrointestinal upset, myalgia, and very
rarely pancreatitis. Further, its efficacy may be
hampered by the presence of a single M184V gene
mutation, which has been observed to confer a high
level of resistance.5
NNRTIs score over PIs, in terms of their better
safety profile, pharmacokinetic features, and ease
of administration. However, a single gene mutation
rendering the NNRTIs impotent is a serious
drawback associated with its use. Furthermore,
the fatal hepatotoxicity associated with NVP’
use requires that close tabs be kept on the initial
treatment regimen.5
Despite these above-mentioned factors, the SLN
has remained as the cornerstone around which the
World Health Organization (WHO)’ guidelines for
ART in resource-starved settings have been built. A
recent study carried out in Cameroon revealed that
the SLN treatment produced undetectable viral load
in 80% of the study subjects. Additionally, the SLN
was well tolerated, with treatment being withdrawn
in only one patient due to the development of
a cutaneous adverse reaction following NVP’
administration.5
Since the current strategies formulated by WHO
are voluntary counselling and testing and provider
initiated testing and counselling which is inadequate
for the control of this communicable disease, there is
a need to develop new strategies by the government.
The reason for no improvement in weight to an
optimal level may be the post HIV depression where
one of the signs of depression is the loss of weight
and another reason is cachexia associated with HIV
infection.
Limitations
This was a retrospective study. After reviewing the
records, we could capture data consistently until 6
months. After 6 months, i.e., at 1-year, 2-year we had
planned to capture the efficacy parameters. Mostly
patients were not adherent to the treatment in our?
hospital but they were referred to higher centres.
Since HIV RNA is not a part of the ART program,
the data could not be captured.
 Navin AP et al: Evaluation of Antiretroviral Therapy
Conclusion
In the present study, there was a significant
improvement in the CD4 counts, the body weight,
and the haemoglobin level when compared to
the baseline, after 6-month treatment with the
combination therapy of stavudine, lamivudine, and
nevirapine. However, there was no difference in
response between severe ill patients (CD4 counts <
200 cells/mm3) and patients with CD4 counts ≥ 200
cells/mm3.
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