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

Update con Aintiwirals

Table 5: Soft Gel Saquinavir and Nelfinavir
Therapy Viral load % below % below CD4+ cell
Regimen drop 400 HIV RNA 50 HIV RNA increases
SGC SQV +
2 NARTIs 1.8 logs 80% 57% 90
NFV +
2 NARTIs 1.6 logs 50% 32% 90
SGC SQV +
NFV 1.5 logs 60% 28% 120
SGC SQV +
NFV + 2 NARTIs 1.8 logs 85% 49% 110

how quickly a person switches when the
initial therapy begins to fail; People who
wait until viral load returns to pre-treatment levels fare less well than those who
switch more quickly (however, those who
switch more quickly also cycle through
their remaining options more rapidly, perhaps hastening the day when no effective
* therapies remain).. what other changes are made when
switching to a dual protease combination;
People who switch without changing their
RT inhibitors or adding new ones (either. nucleside analogue or non nucleoside analogue reverse transcriptase inhibitors) fare
less well than those who do make such. additional changes.

SGC SQV = Soft Gel Caplet Saquinavir

NVF = Nelfinavir

Not surprisingly, analysis of this study
showed that people who had not been on
prior antiretroviral therapy experienced better results than those who had been on previous therapy. Somewhat unexpectedly, the
combination of nelfinavir plus two nucleosides and the combination of SGC saquinavir
+ nelfinavir showed only average and relatively disappointing activity. Furthermore,
people who received the dual protease inhibitor combination experienced more diarrhea than those using only one of the two.
However, no conclusions should be drawn
about the study as it is small and the amount
of data reported thus far is only minimal.

nelfinavir. Six people switched to indinavir
+ NARTIs while the other six switched to
ritonavir + saquinavir + NARTIs. Eight. weeks after the switch, five had no response
or increasing viral loads, four had only a
* transient response and three had a reasonable response sustained for 4 to 8 weeks.
Neither study gives much support for the
claims by the manufacturer ofnelfinavir,
which has argued that people who fail on
nelfinavir will still be sensitive to the other
Sprotease inhibitors. Best case reading of the
two small new studies is that some people
may have a modest response to a second
*protease inhibitor if they use an extremely

elfina ir -powertul combination, like two rotease inViracept~) hibitors together. Even then, it seems unCVrs- e isa c likely to be as large or long lasting as the
Cross R es o cstance response seen when a dual protease inhibiTwo different studies of cross-resistance be- tor combination is used as a first-time
tween nelfinavir and the approved protease therapy. A worse case reading would suginhibitors have produced mixed results. gest that most people wrl have little or no
Cross-resistance is when you have developed. gest a tpeoe il hveitle or no
resitane t onedru whch esuls i reis-response, and there is no evidence of a lastresistance to one drug which results in resis- ing benefit. Overall, the picture of protease
tance to another drug. One of the studies inhibitor cross-resistance continues to sugevaluated 19 people who had increasing vi- gest that all such drugs can induce crossral loads while on regimens containing g
nelfinavir, and were switched to receive. resistance to others of the same type.
ritonavir (400 mg twice daily) + HGC Preliminary results from various studies of
saquinavir (400 mg twice daily) + d4T + protease-protease combinations for people
3TC. People with less advanced disease re-. who are no longer responding to their exsponded reasonably well to this combina- * isting protease inhibitor regimen have shown
tion with about a 1.5 log reduction in viral * mixed results. Generally, factors which inload and an 80 CD4+ cell increase after 12. fluence the outcome include:
weeks (though not as well as people using
the same combination as their initial pro-. U the extent of prior therapy use; The greater
tease inhibitor). By that point, the majority and longer the history of prior therapy
had fewer than 500 copies of HIV RNA.. use, the weaker the response.
People with advanced disease had less ro-. prior use of a protease inhibitor; With few
bust responses. Generally, after 12 weeks exceptions prior use ofanother protease
viral load began to increase toward earlier ib res inseaker s otoa
dual protease combination.
The second study followed 12 people who
also had increasing viral loads while on

Any of these factors can result in less effective and less durable response when switching to a dual protease inhibitor combination. For more discussion of this topic see
the article "Strategies for Protease Inhibitor
Failure" on page 4.
T-20 (pentafuside)
A study with the fusion inhibitor T-20
(pentafuside) has produced some encouraging news, even though it comes from a very
short and very small study. Sixteen people
who had either not been on prior antiretroviral therapy, or who had stopped all
antiretroviral therapy for at least 15 days,
participated in a small dose-escalation study.
The doses studied were 3, 10, 30 and 100
mg (4 participants per dose group) given by
intravenous infusion every 12 hours for 14
days. Little or no antiviral activity was observed at the first three doses. However, the
four people receiving the highest dose had
an average 1.5 log reduction in viral load
and a 52 CD4+ cell increase after two weeks.
Additionally, all four people on the highest
dose saw their viral load drop below the
limit of detection (less than 500 copies of
HIV RNA). Of these four, two had previously used protease inhibitor therapy and
had begun to see their viral loads increase
before they switched to T-20. The other two
in this group had not previously used antiviral therapy. There were no T-20 associated side effects reported, but after such a
short study it would be a mistake to conclude that the drug has no side effects.
To reduce the inconvenience of standard infusion, T-20 is now being given by continuous subcutaneous (under the skin) infusion
from a small, high-tech pump device that
supplies a steady stream of the drug to the
body. Though this drug delivery mechanism
may sound unappealing, it is dramatically
simpler than earlier infusion devices and
many HIV-positive people who have seen

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PI PERSPECTIVE NUIVBER 23 NOVEIVIBER 1997