When to start HIV treatment?

[Guest guest]

Five articles on HIV treatment

1) When to start HIV treatment?

2) Interrupting treatment

3) Premature treatment?

4) New class of drugs called fusion inhibitors

5) What First? Not all treatment combinations are created equal

Jump Start My HAART: When to start HIV treatment?

Information Bulletin #16 - August 2002

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Until recently, the generally accepted way to treat HIV was

aggressively, as soon as the HIV was diagnosed. This approach to

treating HIV was called " Hit Early, Hit Hard " , and it was based on

the belief that you could get rid of HIV from the body with two or

three years of intense therapy. Unless treatment is started within

days of becoming infected, however, no one still believes that HIV

can be eradicated with years of aggressive anti-HIV treatment. In

fact, no one is really certain when the best time to start HIV

treatment is, although the side effects that can develop once

treatment is started have compelled researchers to look at ways to

use powerful anti-HIV drugs when they are needed most.

When is the best time to start on HAART (Highly Active Anti-

Retroviral Therapy)? As we find out more about how HIV works and the

immune system's ability to fight it, official government treatment

recommendations have changed along with our understanding of the

disease. CD4 counts have emerged to be a more reliable signpost,

compared to viral load. As more long-term drug side-effects began to

emerge, and combination therapies continue to improve in terms of

efficacy, the reasons to hold off on starting therapy as long as

possible are convincing. Current treatment guideline says that people

with CD4 counts at or below 350 should consider starting treatment.

Two new studies presented at the Conference this year suggest that

there is possibly even more lead way before starting treatment.

Researchers looked at two groups of people. One group started

treatment when they had between 350 and 500 CD4 cells. The other

group started when they had between 200 and 350 CD4 cells. What they

found was that there were almost no difference between the two groups

in terms of treatment success. Previous studies have clearly shown

that people who start treatment when their CD4 fall below 200 have a

much harder time regaining their health, as well as a higher risk of

disease and death. These and other previous studies make a stronger

case for waiting to start treatment when CD4 falls just above 200.

On the side of caution, however, there was a small study that argues

against delaying therapy. The researchers compared people who started

therapy when they had below 250 CD4 to people who started when they

had above 250 CD4. The results showed that people who started later

had a weaker immune response when they were vaccinated with various

vaccines, suggesting that early treatment may either help the immune

system bounce back to a stronger state, or prevent it from becoming

weaker. A larger and longer study is needed to demonstrate this idea.

It can be scary to live with HIV in your blood and not treat it right

away. It might not be worth all the worrying and second-guessing, and

easier just to jump right into treatment. Many people have done so

and benefited from doing so. Not everyone has severe side effects

from medications. These are decisions that you and your doctor should

carefully discuss. It is important to have your CD4 and viral load

checked on a regular basis and be on the lookout for unusual or new

symptoms that might develop if you decide to hold off on HAART.

020810

TR020803

http://ww2.aegis.org/pubs/atdn/2002/TR020803.html

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HAART Break: Interrupting treatment

Information Bulletin #16 - August 2002

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More information about Structured Treatment Interruptions (STI) was

presented at the conference. There are several different ways

researchers are looking at how best to use this treatment strategy.

They are trying out different lengths of time. One is to stop

treatment for as long as possible until, or if, the virus becomes

detectable or more aggressive. Another is to stop for specific

periods of time, like one-week one treatment, then one week off, then

one week on, etc. There were encouraging, scientifically credible

reports at this conference about Structured Treatment Interruptions

(STI).

Three reports were especially interesting. Researchers at The s

Hopkins University in Baltimore, land studied 75 people with an

average of 677 CD4 cells and an average viral load of 263 who were

taking a treatment regimen (HAART). The point of the study was to

have people stop taking treatment, and see how long it took until

their CD4 count dropped down to around 200. After 30 weeks, twenty-

three people (31%) went back on treatment. After sixty-nine weeks,

there were still fifty-two people (69%) who had not restarted

treatment.

When looking at the difference between the two groups, the

researchers found that people who had higher CD4 counts when they

first started on HAART were able to stay off treatment longer. People

with higher CD4 counts lost 115 CD4 cells a year, meaning that they

could possibly take a four-year treatment break until they needed to

restart treatment. The people who had lower CD4 counts when they

started HIV treatment in the first place had to restart treatment

earlier because they had an average decline of 314 CD4 cells per

year. This study is good news for people who started treatment with

high CD4 counts. An STI may be a useful treatment strategy for them.

It was estimated that the other people in the study with lower CD4

cells could safely stay off treatment for about 8 months, a lengthy

drug holiday.

Pulse Therapy is another approach being studied. People take their

HIV meds for one week, then stop taking them for one week, then start

taking them again the next week. It has been shown that the virus

doesn't have enough time to bounce back in 7 days during studies of

this type of STI. Mark Dybul from the National Institute of Health

looked at a small group of people whose viral load was undetectable,

taking either of two combinations: d4T, 3TC, indinavir/ritonavir, or

ddI, 3TC, efavirenz. After one year of pulse therapy, none lost

control of their virus. At the same time, there was improvement in

their blood lipids (fat) levels.

There is also a strategy called Stop and Switch. There were some

surprising results presented from a French study call GigaHAART. The

researchers worked with a group of people with high viral loads that

their treatments were unable to control. In the study, one group of

people started on an eight (8) drug regimen of Zerit, Videx, Ziagen,

Epivir, a non-nucleoside reverse transcriptase inhibitor (NNRTI) and

three (3) protease inhibitors. The other group stopped treatment

altogether for eight weeks, after which they started taking the

GigaHAART. The researchers found that 50% of the people who stopped

before switching were able to get a one log drop in viral load,

compared with only 24% participants who switched without stopping.

These results conflicted with an earlier Spanish study that found no

difference between the two groups. It is not clear what the reason is

behind the different findings.

These approaches are based on recent scientific findings that lend

support to the concept of STIs, but still leave a large number of

questions unanswered. Are they safe? Will they lose the gains someone

has already made against the virus? Will HIV seek out other

compartments or cells in the body? Is the drug resistant virus really

gone, or is it just lying low in hostile territory?

Unfortunately, drug toxicities and long term side effects begin to

increase the longer the drugs are taken. They can damage body organs,

disrupt metabolism and cause strange and unpleasant body shape

changes, and increase fat in the blood to dangerous levels. The main

cause of AIDS related deaths in the US today is liver failure, which

is attributed not only to co-infection with hepatitis viruses,

smoking, obesity, and alcohol use, but also the side effects of anti-

HIV meds. The side effects and potentially serious conditions that

can occur from the use of HIV meds - including diabetes, metabolic

disorders, heart disease, etc. - is driving the research to limit

exposure to anti-HIV drugs only for as long as they are needed.

Not having to take any medications on an everyday basis is what many

people really want. But no scientific research supports taking HIV

meds whenever you feel like it as an effective treatment strategy,

and the new drugs are just not here yet. Researchers are trying their

best to determine if there is an orderly, safe, and effective way to

give treatment and side effect weary people a break. The fact that

many people with HIV struggle to come up with the cash to cover what

the doctor ordered is a factor that may leave them no other option

but to interrupt continuous therapy.

On top of all these factors, taking medications every day on a

scheduled basis can lead to burn out. One study at the conference

reported that people with HIV prefer to take simpler drug combination

of fewer pills, preferably once or twice a day. They would also like

not to experience any side effects from any of the treatments they

take. People with HIV would like less toxic and more convenient

treatments that control HIV. New formulations of drugs, some taken as

one pill once a day, may help ease some of the burden, but not

necessarily the side effects.

Again, these are promising but preliminary results. There are even

more studies of STIs taking place that give participants drugs such

as interleukin-2 or a vaccine while they are off drug, but there are

no clear answers at this point. Much remain unknown about the long-

term outcome of these approaches to HAART. If you are having problems

with staying on HAART, these results do seem to provide you with some

encouraging options. However, don't try it on your own. Talk to your

doctor about it. It may allow you to recover your strength and

determination to start taking the same or other medications with

fewer problems.

Some drugs and drug combinations are the wrong choices for an STI. If

you feel that you can't discuss your treatment options frankly with

your doctor and need some coaching or a referral, contact The Network

Case Management Program at (800) 734-7104.

020810

TR020805

http://ww2.aegis.org/pubs/atdn/2002/TR020805.html

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Stop This Train, I Want to Get Off! Premature treatment?

Information Bulletin #16 - August 2002

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What about those people who started treatment according to earlier

guidelines? This is a thorny question many medical providers are

struggling to answer. A small study took it up in Argentina. 28

people who started their HAART with CD4 counts above 350 and viral

load below 60,000, with at least 6 months on HAART and current

undetectable viral load stopped their treatment. An initial drop in

CD4 was seen after stopping, but after a few weeks the number climbed

back and stabilized close to levels before stopping, at 12 weeks

average CD4 is 544, compare with 610 at start of trial. At week 24,

viral load stayed within one log of their pre-treatment levels. An

improvement in cholesterol levels was seen. The trial was design to

re-start treatment if a participant's CD4 dropped below 350 twice in

a role, so far, none have restarted at 24 weeks.

These results suggests that stopping therapy might be an option for

people who have their HIV under control and high CD4 counts,

especially if you are having problems with drug side-effects. Keep in

mind that this is a small study, done with very careful monitoring

and with people in a very specific situation. This study has also

only been going on for 24 weeks, at this point not much is known

about possible long-term repercussions of stopping treatment,

particularly the possibility of drug resistance. If you are

considering stopping HAART, don't do it on your own. You need to work

with your doctor and look closely at your current health status, as

well as your past experience on HAART. It can be tempting to just

flush the pills down the toilet, but make sure you are not

jeopardizing your chances down the road.

020810

TR020804

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http://ww2.aegis.org/pubs/atdn/2002/TR020804.html

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A Brand New Heavy T-20 on center stage

Informatin Bulletin #16 - August 2002

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The big HIV treatment news this year is the drug T-20. This drug is

in a brand new class of drugs called fusion inhibitors. The drug

stops HIV from fusing with a cell and infecting it, preventing the

virus from taking over the cell and setting up an HIV factory. This

drug blocks HIV at a different point of infection than every other

existing drug. This is a critical development for people who have HIV

that is resistant to existing HIV drugs, and for people who just

can't tolerate those drugs. T-20 is administered by injection twice a

day. FDA approval of the drug is expected to come soon, and another

round of the Expanded Access program described below is expected to

start within a few months. The positive results described in this

article offer much needed hope for people who have run out of

treatment options, as well as people who are getting to that point.

Two Phase III trial results were presented at the Conference. Both

had 500 or so people who had previously tried most other HIV

treatments. On average, the study participants had taken 12 drugs,

for an average of seven years. The average CD4 count of the people in

these studies was 80. Eighty-seven percent (87%) of the participants

had an AIDS defining illness. The median viral load was 5.2 log or

about 150,000. People in the study were given T-20 in addition to 3

to 5 other HIV drugs that were chosen based on their treatment

history and levels of resistance to those drugs. Although some people

may be resistant to a specific HIV drug, the level of resistance may

not be so high that the drug is worthless against HIV.

Although ninety-eight (98%) of participants in these study had an

injection site reaction, no other major side effects were reported.

Minor side effects such as headaches were reported in a small

percentage of the participants. In all 11% to 17% of the people who

joined the study discontinued for various reasons. After 24 weeks, a

drop of -1.7 and -1.4 log in viral load were seen in the two studies.

Fifty-two (52%) and forty-three percent (43%) of participants in the

two studies had more than 1 log viral load decrease. In one study

thirty-seven (37%) of participants, and in the other study twenty-

four percent (24%) reduced the level of HIV in their blood to an

undetectable amount (under 400).

According to the drug companies Trimeris and Roche, there is a large

batch of the drug undergoing safety, stability and shelf life testing

in their Colorado plant. The earliest possible available date for

another round of the T-20 Expanded Access Program is most likely

October of 2002. If you are in need of a salvage therapy such as T-

20, you should start talking about it with your doctor now. Expanded

access programs can be a very involved process, and your doctor must

participate in the program in order for you to get such drugs. If you

need further help you could enroll in The Network's Case Management

program.

020810

TR020802

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What First? Not all treatment combinations are created equal

Information Bulletin #16 - August 2002

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Given the limited number of drugs currently available to treat HIV

infection, clinicians and researchers have been trying to find out

which drugs work best as a first treatment combination. Current US

treatment guidelines recommend using two NRTIs (Zerit, Videx, Epivir,

Zidovudine, etc.) and one protease inhibitor or protease combination.

Another option is using two NRTIs and a non-nucleoside (NNRTI) such

as Sustiva.

Apparently, not all drugs are created equal. Several studies

presented at the conference indicated a winning combination: AZT, 3TC

plus efavirenz (Sustiva). Previous trials have shown that efavirenz

is more potent than indinavir (Crixivan) when used as a first line

therapy. This time, researchers compared efavirenz (Sustiva), a Non-

Nuke, to nelfinavir (Viracept), a Protease Inhibitor, in combination

with two different NRTI combinations, AZT + 3TC versus. ddI + d4T, as

well as a four drug combination with different NRTIs.

The three-drug combination of AZT, 3TC, and efavirenz was shown to be

significantly more potent, with less drug toxicity. These studies

were designed before the approval of lopinavir (Kaletra) and

tenofovir (Viread). Studies comparing these new drugs are sure to

come in the future. An important note of caution is that NNRTIs are

known to be easier for HIV to develop resistance to than protease

inhibitors. Sustiva also has distinct side effects that might make

Viramune (nevirapine) a better choice in certain cases. These issues,

and several others, especially your mental health, life-style and

ability to actually stick to a regimen should go into deciding a

first regimen. Unless you have very low CD4 cells and symptoms of HIV

disease, you probably have some time to carefully consider your first

regimen, and when you should start it.

020810

TR020806

http://ww2.aegis.org/pubs/atdn/2002/TR020806.html

Copyright © 2002 - AIDS Treatment Data Network. Reproduction of this

article (other than one copy for personal reference) must be cleared

through the AIDS Treatment Data Network. Email: network@...

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Cross posted from JVNet.

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