Perspective: Information, Inspiration and Advocacy for People Living with HIV/AIDS

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Update on Antivirals
Research into anti-HIV therapy is producing hopeful results
almost weekly. Yet some issues remain stubbornly difficult to
address. Studies have shown that many people, by starting at
least two new potent drugs (generally from classes of drugs that
they haven't used before) in their combination therapy, can
achieve sustained suppression of HIV. Yet it is also likely that
starting only one drug that is potent by current standards will
lead to only short-term benefit.

Overall it is very important to develop a
long-term strategy that is well tolerated, has
a reasonable dosing schedule, includes two
highly potent therapies and leaves other
treatment options open if a change of
therapy is necessary. While these sound like
simple rules, they are often difficult to
implement because of the limited number
of new drugs available and because of crossresistance between those already available.
One possible improvement is that new drugs
now being developed generally have a more
favorable dosing schedule (either taken once
or twice daily) which makes them a more
desirable choice for people starting therapy
for the first time. However, there is still very
little information available to guide the
choice of a second or third treatment regimen after an initial combination loses its
ability to suppress viral replication. Real
and lasting progress in this area will re
quire not only more new drugs but new
classes of drugs that work no matter what
treatments a person has used previously.
I Efavirenz (DIVIP 266,
Sustiva~)
A recent study indicates that the combina* tion of the non-nucleoside reverse transcriptase inhibitor efavirenz and the protease inhibitor indinavir (Crixivan@) con* tinues to show potency after 48 weeks. One
hundred and one people with CD4+ cell
* counts ranging from 100 to 500 and HIV
* RNA of greater than 20,000 copies particiI pated in this study. The majority of the
volunteers had previously been on nucleoside analogue reverse transcriptase inhibitors (NARTIs), such as AZT or 3TC. They
received either indinavir alone (42 people)
* or indinavir + efavirenz (59 people). Dur* ing the study, the doses of both drugs were

adjusted to improve potency. The dose of
efavirenz was initially 200 mg once a day,
but after 36 weeks this was raised to 600
mg daily because the higher dose may have
better antiviral activity. The dose of. indinavir was increased from 800 mg to
1000 mg every 8 hours after data indicated
that efavirenz decreases indinavir levels by
about 30%. After 12 weeks of the study,
people receiving indinavir alone, were
switched to receive indinavir + efavirenz +
d4T to reduce the possibility of resistance
developing to indinavir. The results after
48 weeks are shown in Table 1.
* These are clearly some of the most impres-. sive two-drug combination results observed
to date and challenge the current idea that
people have to be on at least a 3-drug
combination. The dose of efavirenz used in
other studies has been increased to 600 mg
once daily. Efavirenz was generally well tol* erated. Reported side effects included rash,
headache, diarrhea, dizziness and nausea.
I Indinalvir (Crixivan~)
Important new information from the long* running Merck 035 study has been reported.. This study, which we have previously reported, included 97 people with average
CD4+ cell counts of 144 and HIV RNA
levels of about 43,000 copies. They received
* indinavir alone, AZT + 3TC or AZT + 3TC
+ indinavir. After 24 weeks everybody was
switched to the 3-drug regimen. Everybody
had used AZT extensively before entry
(about 85% had developed resistance to
* AZT) and about 80% had also been on. prior ddl, ddC or d4T. However, all were
* using 3TC and a protease inhibitor for the
first time. After following the group for two
years, 81 % of those who started with the
3-drug combination continue to have fewer
than 500 copies of HIV RNA. However, of
those who originally received indinavir
alone or AZT + 3TC only 36% and 40%
respectively now have fewer than 500 copies of HIV RNA, even though after 24
weeks they were switched to the 3-drug
combination. Similarly, after 2 years of the
study, there was an average 2 log reduction
* in HIV RNA for people originally receiving.the 3-drug combination, 1 log reduction for.those receiving AZT + 3TC and a 1.2 log
* drop for people starting on indinavir alone.
Additionally, after 2 years of the study there
* was a median 230 CD4+ cell increase. among people originally receiving 3-drug
*therapy, versus a 100 CD4+ cell increase.for people on AZT + 3TC and a 110 CD4+
-cell increase for people on indinavir alone.
* The results are shown in Table 2.

Table 1: Indinavir and Efavirenz

Therapy Viral load % below 400 CD4+ cell
Regimen drop copies HIV RNA increase
IDV + EFV 2.38 logs 88% 240
IDV (12 wks, then)
IDV + EFV + d4T 1.89 logs 68% 150 j
IDV = Indinavir EFV = Efavirenz
Table 2: Merck 035 at Two Years
Therapy % viral load Average in Average
Regimen below 500 reduction increase in
copies viral load CD4+ cells
Started IDV +
AZT +3TC 81% -2logs + 230
Started IDV,
at 24 wks added
AZT + 3TC 36% - 1.2 logs + 110
Started AZT + 3TC,
at 24 wks added IDV 40% - 1 log + 100

IDV = Indinavir

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PI PERSPECTIVE NUIVBER 23 NOVEIVBER 1 997