E-DRUG: Access to Kaletra in developing countries
[E-drug does not normally discuss patient cases, but this case from Ethiopia
has maybe some general interest points. WB]
I present a case to share with you on a person living with HIV and on ARV
The drugs for the first regimen were zidovidine lamivudine and nelfinavir
(viracept). At the time the therapy started the drugs were obtained from the
black market which was the only option. In the middle there was problem in the
availability nelfinavir (Viracept) and it was shifted to efavirenz (Stocrin).
Then the Ethiopian government started antiretroviral therapy as a program in
selected sites but unfortunately efavirenz was not available in the program and
the physician shifted to nelfinavir a year ago.
After four months, the therapy CD4 started to decline and before 15 days the
viral load was extremely high indicating that resistance had developed. The
doctors suggested that the only option that is left to be to use lamuvidine,
viread and combination of lopinavir and ritonavir (Kaletra).
I discussed this issue with e-drugger Dr Valeria whom I have known on e-drug to
help on this issue. She responded quickly and helped a lot on the issue. I
would like to thank her for the effort that she exerts to help me find the
right track. The Abbott Labs have got a program for these drugs for people
living in poor countries with a price with no profit. I have send message-about
the case but they have not responded yet. I am afraid that the programs in
Ethiopia may not include these drugs.
Dear e-druggers at this point I would like to raise two questions:
First what alternatives are available for the case mentioned above other than
the new PI?
Second on how people in developing countries who are in need of these drugs
could get access to the drugs if the drugs are not included in the existing
programs? I feel that this could be question of thousands living in poor
Finally I would like to summarize some tips which could have relevance with the
case I mentioned above.
HIV reproduces itself very quickly and when reproducing often makes slight
mistakes. So each new generation, or new strain, of HIV differs slightly from
the one before. These tiny differences in the structure of HIV are called
mutations. Some of the mutations occur in the parts of HIV which are targeted
by anti-HIV drugs. So although you have some HIV that continues to be affected
by the drugs, you have other strains of HIV that are not affected by the
anti-HIV drugs as effectively as before. This HIV is called drug resistant HIV,
and it is then able to reproduce unaffected by the drugs.
When someone has drug resistant HIV (commonly referred to as drug resistance),
the amount of HIV in the blood rises and the risk of the person becoming ill
increases. Drug resistance is one of the main reasons why antiretroviral
treatment fails. If resistance to the current drug treatment is developed, this
usually means that the drug regime needs to be changed.
The anti-HIV drugs work the best when used the first time. This is one of the
reasons why it has to be considered carefully whether a change of treatment is
necessary or not. The combination of anti-HIV drugs other than the first or
second treatment is called salvage therapy. It is also referred as second-line,
third-line or rescue therapy.
Monitoring the viral load carefully is an important part of treatment. There
are different opinions about the 'right time' to change the treatment if your
viral load is rising. Some doctors recommend changing the treatment as soon as
the viral load starts to rise. Others recommend monitoring the overall trend of
the viral load before making a decision to change. Changing the drugs earlier
rather than later, could mean running out of treatment options quicker. But
changing later, means there is a danger of developing resistance to certain
drugs. This can seriously limit your future treatment options. The changes that
can be made to the drug regime will depend on the drugs already being used, the
CD4 count and your general health.
Many people start their salvage therapy with much higher levels of viral load
than previous treatments. This puts more pressure on the new combination to
work. Each combination used lessens the chance of maintaining a low viral load
because of the possibility of developing resistance to the drugs. The choice of
new treatment should always depend on what caused the previous one to fail.
New antiretroviral drugs (drugs in existing classes with activity against
resistant strains, or new drug classes with novel mechanisms of action)
including those available on expanded access or through clinical trials may be
According to release from Abbot in a study of individuals with extensive
nucleoside analogue and protease inhibitor experience (but no prior NNRTI
experience) and virologic recurrence on treatment, changing to a regimen
including lopinavir/r and efavirenz resulted in viral load suppression at week
24 in the majority of participants.The effectiveness of regimens containing
lopinavir/r in patients with prior NNRTI experience and failure of a protease
inhibitor-containing regimen is unknown.
Data from the randomized, uncontrolled, prospective Phase II study of 100
treatment-naove patients taking Kaletra in combination with lamivudine (3TC)
and stavudine (d4T) show that of 17 patients out of 27 patients who met the
criteria for resistance testing with resistance data available through 252
weeks, none demonstrated evidence of resistance to lopinavir (0/17) or
stavudine (0/17). Three patients (3/17) Demonstrate damivudine esistance.
In addition, 64 percent of patients (64/100) had an undetectable viral load
(HIV RNA less than 50 copies per milliliter) and 67 percent (67/100) had HIV
RNA less than 400 copies per milliliter, using an intent-to-treat (ITT)
analysis, which categorizes any patient who does not complete the study as a
treatment failure. Of the 68 patients remaining on treatment (OT) at week 252,
94 percent (64/68) of patients had an undetectable viral load and 99 percent
(67/68) had HIV RNA less than 400 copies per milliliter.