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| PRODUCT DETAILS |
DESCRIPTION
Duovir-N is a combination of 3 drugs commonly used in
the management of Human Immunodeficiency Virus (HIV) infection.
Both zidovudine and lamivudine belong to the nucleoside
analogue class of antiretroviral drugs. Both drugs act
by terminating the growth of the DNA chain and inhibiting
the reverse transcriptase of HIV. Nevirapine is a non-nucleoside
reverse transcriptase inhibitor. It acts by directly inhibiting
reverse transcriptase.
Each tablet of Duovir-N contains half of the commonly
prescribed daily doses of zidovudine, lamivudine and nevirapine.
All three drugs are to be administered twice daily irrespective
of meals, permitting a fixed-dose combination to be formulated.
With the availability of this combination formulation,
patients may be better able to adhere to triple drug regimens,
thereby enhancing compliance and ensuring the success
of antiretroviral therapy.
COMPOSITION
Duovir-N
Each film-coated tablet contains
Lamivudine 150 mg
Zidovudine 300 mg
Nevirapine 200 mg
PRESENTATION
Duovir-N Container of 30
tablets
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| BACK |
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| CLINICAL EFFICACY OF ZIDOVUDINE
+ LAMIVUDINE + NEVIRAPINE |
STUDY
1 - THE COMBINE STUDY
a) Virologic and immunologic efficacy
Study Design
Randomized, open-label, multicentre study
Number of patients
142
Regimens
Nevirapine + Zidovudine + Lamivudine or
Nelfinavir + Zidovudine + Lamivudine
Duration
1 year
Population
Antiretroviral-naïve patients |
| Baseline parameters |
| Mean viral load (copies/ml) |
5.15 log (range 3.2 - 6.2) |
| Mean CD4+ cell count (cells/mm3) |
359 (range 10-906) |
- One third of patients had viral load > 5 logs
- 20% had CD4 count < 200 cells/mm3
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| Results at 1 year |
|
Type of
analysis
|
HIV RNA
< 200 copies/ml
|
HIV RNA
< 20 copies/ml
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|
Nevirapine
Group
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Nelfinavir
Group
|
p value
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Nevirapine
Group
|
Nelfinavir
Group
|
p value
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Intent-to-treat
(missing=failure)
|
75%
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60%
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0.056
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65%
|
50%
|
0.065
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| On-treatment |
92%
|
81%
|
0.012
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80%
|
71%
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0.35
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- No differences were observed when comparing efficacy
rates in the sub-group of patients with baseline viral
load > 5 logs.
- An increase of 173 cells/mm3 was observed in the
nelfinavir group, whereas an increase of 162 cells/mm3
was observed in the nevirapine group (not significant).
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| Conclusion |
| This study concluded that
a nevirapine-containing regimen has at least similar efficacy
to a nelfinavir-containing regimen. Both regimens have
an acceptable tolerance. A simple 4-pill nevirapine-based
regimen may be an excellent option for HIV-infected patients
who initiate antiretroviral therapy. |
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b) Lipid substudy
In a subgroup of 43 patients (20 on nelfinavir, 23 on
nevirapine), body composition changes and metabolic
alterations were compared. Mean serum levels of LDL
increased significantly (p<0.05) from 3.11 to 3.64
mmol/L in nelfinavir-treated patients and remained stable
in nevirapine-treated patients. Prevalence of patients
with LDL levels >3.36 mmol/L increased in the nelfinavir-treated
group and decreased in the nevirapine-treated groups
as shown below:
In the nelfinavir group, a 1.41-fold increase
in triglycerides (from 1.52 to 2.15 mmol/L) was noted,
whereas in the nevirapine group the mean triglyceride
value declined from 1.64 to 1.56 mmol/L. At follow-up,
significant differences (p<0.05) in HDL (1.28 vs
1.57 mmol/L) and HDL: TC ratio (0.24 vs 0.31, respectively)
occurred.
In conclusion, a trend to a more atherogenic lipid
profile was observed in the nelfinavir-treated group,
as compared to the nevirapine-treated group.
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c) Immune restoration
36 patients (16 receiving nelfinavir, 20 receiving nevirapine)
were enrolled in an immunological substudy. A significant
increase in CD4+ T-cells was observed in both groups
at 1 year. Book regimens were similarly effective in
reducing activated T-cells. A significant increase of
both CD4+ and CD8+ CD28+ T-cells occurred in both arms
of treatment. Patients of both regimens showed a significant
decrease of activated memory CD8+ T-cells and a clear
increase of naive CD8+ T-cells. Perepheral blood mononucler
cells (PBMC) proliferative responses to cytomegalovirus
antigen increased significantly in both groups.
Thus, similar degrees of immune restoration were
observed at the end of 1 year in both the groups. This
reinforces the role of nevirapine-containing regimens
as a valid option for initiating antiretroviral therapy.
d) Virological response in reservoirs
A substudy evaluated the virological response of
the 2 regimens in tonsillar lymphoid tissue, cerebrospinal
fluid and semen. Comparable results were obtained.
Ref: 1st International AIDS Society Conference, July
2001
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| STUDY
2 |
Study Design
Randomised double-blind placebo-controlled study
Duration
64 weeks
Number of patients
171
Regimens
Nevirapine + Zidovudine + Lamivudine (n=77)
Placebo + Zidovudine + Lamivudine (n=94)
Population
Antiretroviral-naïve patients with advanced HIV disease
and high viral loads
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| Baseline parameters |
| Parameter |
NVP + ZDV +
3TC (n=77) |
Placebo + ZDV
+ 3TC (n=94) |
| Mean viral load (copies/ml) |
138,000 |
148,000 |
| Mean CD4 count (cells/mm3) |
101 |
93 |
- Nevirapine patients with high viral loads
- 51% > 100,000 copies/ml
- 30% > 500,000 copies/ml
- Nevirapine patients with low CD4 cell counts
- 52% < 100 cells/ mm3
- 27% < 50 CD4 cells/ mm3
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| Results |
- After 64 weeks, 77% of patients taking NVP + ZDV
+ 3TC had viral loads < 400 copies/ml
- The sustained antiviral response was not influenced
by baseline viral load (p= 0.797)
- The sustained antiviral response was also statistically
significantly correlated with baseline CD4 count (p=
0.0049)
Proportion of patients in NVP+ZDV+3TC arm with undetectable
viral loads
<50 copies/ml at 48 weeks stratified by baseline
viral load:
Missing = Failure
Proportion of patients in NVP+ZDV+3TC
arm with undetectable viral loads
<50 copies/ml at 48 weeks stratified by CD4 cell
count:
Missing = Failure
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| Conclusion |
- The regimen of zidovudine + lamivudine + nevirapine
was as effective in patients with high viral loads
as in patients with low viral loads.
Ref: 7th Conference on Retroviruses and
Opportunistic Infections, San Francisco,February
2000, Abstract 517
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