IMPORTANT
DUOVIR-N IS NOT INTENDED
FOR USE IN PATIENTS WHO ARE JUST INITIATING THERAPY WITH
NEVIRAPINE. DUOVIR-N SHOULD BE ADMINISTERED ONLY TO PATIENTS
WHO HAVE RECEIVED ZIDOVUDINE + LAMIVUDINE (STANDARD DOSES)
+ NEVIRAPINE (200 MG OD) FOR 2 WEEKS AND HAVE DEMONSTRATED
ADEQUATE TOLERABILITY TO NEVIRAPINE (SEE INDICATIONS,
DOSAGE AND ADMINISTRATION) |
|
| ANTIRETROVIRAL THERAPY:
AN OVERVIEW |
The goal of antiretroviral therapy is
to maximally suppress HIV replication, so as to preserve
immune function, reduce the incidence of opportunistic
infections, retard disease progression and prolong
disease-free survival.
Currently available antiretroviral drugs inhibit HIV
replication at two steps in the viral life cycle.
The life cycle is shown in the diagram below.
1. HIV enters a CD4 cell.
2. HIV is a retrovirus, meaning that its genetic information
is stored on single-stranded RNA instead of the double-stranded
DNA found in most organisms. To replicate, HIV uses
an enzyme known as reverse transcriptase to convert
its RNA into DNA.
3. HIV DNA enters the nucleus of the CD4 cell and
inserts itself into the cell's DNA. HIV DNA then instructs
the cell to make many copies of the original virus.
4. With the help of the protease enzyme, new virus
particles are assembled. These newly formed viruses
leave the cell, ready to infect other CD4 cells.
Thus, protease inhibitors target the protease enzyme,
whereas reverse transcriptase inhibitors target the
reverse transcriptase enzyme. Reverse transcriptase
inhibitors are further divided into two types - nucleoside
reverse transcriptase inhibitors and non-nucleoside
reverse transcriptase inhibitors - based on slight
differences in their chemical structure and mode of
action.
| Nucleoside
reverse transcriptase inhibitors (NRTIs) |
Non-nucleoside
reverse transcriptase inhibitors (NNRTIs) |
Protease
inhibitors (PIs) |
| Zidovudine (AZT) |
Nevirapine |
Saquinavir |
| Stavudine (d4T) |
Efavirenz |
Ritonavir |
| Lamivudine (3TC) |
Delavirdine |
Indinavir |
| Didanosine (ddI) |
|
Nelfinavir |
| Zalcitabine (ddC) |
|
Amprenavir |
| Abacavir |
|
Lopinavir/ritonavir |
|
In an asymptomatic patient, international guidelines recommend
that antiretroviral therapy should be initiated when CD4
count goes below 350 cells/ l or HIV RNA is above 30-55,000
copies/ml. All symptomatic patients should be offered
antiretroviral therapy irrespective of CD4 counts or plasma
viral load.
It is recommended that a minimum of 3 drugs be used to
initiate antiretroviral therapy. This triple regimen should
contain 2 NRTIs with 1 NNRTI or 1 PI.
Recommended antiretroviral drug regimens are depicted
in the following table - the regimen should consist of
1 choice each from columns A and B. |
| Column A |
Column B |
| Efavirenz |
Stavudine + didanosine |
| Indinavir |
Stavudine + lamivudine |
| Nelfinavir |
Zidovudine + didanosine |
| Nevirapine |
Zidovudine + lamivudine |
| Ritonavir + indinavir |
Didanosine + lamivudine |
| Ritonavir + lopinavir |
Zidovudine + zalcitabine |
| Nelfinavir + saquinavir SGC |
|
| Saquinavir SGC |
|
| Abacavir |
|
| Amprenavir |
|
| Delavirdine |
|
| Ritonavir |
|
|
Even if triple therapy is
used, over a period of time, there is a possibility of
the virus developing resistance and the patient failing
his initial treatment regimen. Hence, the initiation of
antiretroviral therapy should be viewed as the beginning
of a longer term strategy.
If, for example, a patient has started therapy on a PI-based
regimen and is no longer responding to this regimen, his
second-line regimen may include an NNRTI-based regimen,
and vice versa. It is recommended that the second-line
regimen should ideally contain 3 drugs to which the patient
has never been exposed. |
| BACK |
| |
|
| NNRTI-BASED REGIMENS AS
FIRST-LINE OPTIONS |
|
Several factors need to be considered when choosing
between NNRTI-based and PI-based regimens. These are:
- Potency and durability of a specific regimen
- Toxicity profile of the agents under consideration
- Complexity of the dosing schedule
- Potential drug interactions
- Potential for cross-resistanc
- Cost and access to antiretrovirals
The advantages of an NNRTI-based regimen (such as nevirapine)
are as follows:
- Better patient compliance due to a lower pill burden
as compared to PIs. Moreover, the availability of
certain fixed-dose formulations containing nevirapine
has further reduced the pill burden, to just 1 pill
twice daily.
- Dosing irrespective of food.
- No long term toxicities as seen with PIs, such
as elevated cholesterol and triglycerides, osteopenia,
insulin resistance and lipodystrophy.
- Proven to be as effective as PIs.
- Spares the use of PIs for a later date.
- Lower possibility of drug interactions as compared
to PIs.
- NNRTI-containing regimens are more affordable.
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