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AIDS Therapy in the New Millennium

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Feb. 1, 2001 -- Two things are being left behind as AIDS therapy marches into the new millennium. Gone -- for those with access to anti-HIV drugs -- is the despair of the days when AIDS meant death. Gone, too, is the fervent hope that drugs can cure HIV infection.

"There is no way this phase of the AIDS epidemic -- in the U.S. -- will be anything like the first phase of the epidemic -- it will be a fraction of what we saw then," leading AIDS researcher John W. Mellors, MD, tells WebMD. "Some people are going to do great, but some are going to slip through our hands. It is going to be this way for a long time. We will edge up, then fall behind."

It seems like only yesterday -- actually it was the mid-1990s -- when the advent of potent triple HIV therapy held out the promise that HIV could be cured. Researchers calculated that only a few years of highly active antiretroviral therapy (HAART) could wipe out the AIDS virus. They were wrong.

Only two years ago, many of his peers thought University of California at San Francisco researcher Jay Levy had flipped his lid when he publicly rejected the cure-oriented "hit hard, hit early" approach to AIDS therapy. Now the same scaled-back approach he advocated then will soon be enshrined in official AIDS therapy guidelines. These new guidelines will reflect a more sober mood among doctors whose goal now is to extend the benefits of therapy -- and to minimize its toxic side effects -- for as long as possible. They advise holding off taking AIDS drugs until blood tests show that a person's immune system is beginning to fail.

"The new era we are in is 'hit early is wrong' -- that approach was not based on the understanding you would have to treat people for so long," Levy tells WebMD. "It is a matter of time before the drugs no longer work. That is what we are learning. If you start too early, your options are used up. It is predictable. Drugs are running out, and we don't have anything great on the horizon."

Levy -- one of the first researchers to isolate the virus that causes AIDS -- thinks future guidelines will go even further, holding off treatment until the immune system is on the verge of collapse or until AIDS symptoms begin to appear. "Now we are saying let's wait until a person develops symptoms and the drugs really will help," he says.

And it's not just a matter of side effects. If a person takes AIDS drugs long enough, drug-resistant strains of HIV eventually will appear. This means switching drugs again and again until there aren't any more drugs left to take. Many patients already have reached this stage.

"This is a heartbreaking group to deal with," says Mellors, chief of the division of infectious diseases at the University of Pittsburgh School of Medicine. "What will be required for them is access to multiple [experimental drugs]. ... But we have a significant waiting time for a lot of people. I have people I would love to put on these drugs right now, but they have to wait."

Atlanta AIDS clinician Kimball Johnson, MD, has been treating patients since the early days of the epidemic. She agrees with Mellors that the bad old days are gone -- but that some patients are at the end of their ropes.

"I started my AIDS practice with 14 people in the hospital at a time," Johnson tells WebMD. "This past year, I saw only one death, although last year I had some patients who had been around since the beginning of the epidemic who had run through all of their options. They began single-drug therapy with AZT, and then sort of had serial monogamy with one drug after another until they got resistant to every single drug. Those are the ones we are seeing funerals with."

Mellors says it isn't simply a matter of who began with single-drug therapy -- what counts is whether anti-HIV drugs can suppress the AIDS virus.

"Some patients who went on monotherapy and switched to triple therapy are fine, and some who started with triple therapy are having some problems," he says. "In our clinic, 60% of patients do well -- they have undetectable virus. About 40% of these patients who have been put on anti-HIV drugs have delayed toxicities that result in changes in their bodies -- wasting of the face and limbs and central accumulation of fat -- and additional longer-term toxicities that include bone loss and increased risk of [heart] disease. But in terms of their HIV infection, they are doing well: Their virus is suppressed, and they have recovery of immune function."

Recovery of immune function is the key to the future of AIDS therapy. Most patients who receive anti-HIV drugs regain strong immune responses -- but for reasons that remain unknown, these immune responses do not work against HIV itself.

"What you have to do is boost the immune system -- that is really the secret to controlling this virus," Levy says. "You might do it by immunization, but we don't have a good vaccine. Or the more recent emphasis is going to be on structured treatment interruptions, where you stop the drugs for a while, let the virus come back up so the immune system can get a look at it, and then restart the drugs again. And [the immune-boosting substance known as] IL-2 has regained popularity." He explains that IL-2, when given with HAART, increases infection fighting cells, but unfortunately, they don't target the HIV. "Now the question is how to program those returning cells to fight HIV," he says

These medical questions are not the only clouds looming on the HIV horizon. Atlanta's Johnson says that for the first time in a long time, she is seeing a steady increase in people newly infected with the AIDS virus.

"It is alarming that we are seeing a resurgence of new HIV diagnoses," Johnson says.

Mellors predicts that he will see the same thing. "We are seeing a resurgence of HIV risk behaviors so it is only a matter of time," he says. "I don't want to sound pessimistic, but it is almost predictable that we have great resources and motivation as human beings for only a short period of time. It's our attention span. This is the same thing that occurred with tuberculosis -- absolutely the same thing. It will be two steps forward and one step back -- that is the story in most infectious diseases. For global control of AIDS, we are really talking about the need for an effective vaccine. This is not to say that for individuals the drugs can't have great benefit -- but for the disease as a whole, it will be to and fro for a long time to come."

* The Delaware HIV Consortium Web Site
- Provides a variety of resources to individuals searching for information on HIV/AIDS, including private counseling, support groups for individuals and their families, nutritional guidance, a resource library, treatment education and links to other local, national and international HIV Internet resources.

* Oregon Health Division's HIV Program
- Contains info on AIDS/HIV, such as the Weekly AIDS Surveillance Report, prevention calendar of events, and more.

AIDS information & treatments from Johns Hopkins University

* AIDS-HIV Internet Resource Center
- Extensive list of sites, as well as an HIV/AIDS bookstore.

* The NAMES Project AIDS Memorial Quilt Website
- Get information on the quilt (how to add, countdown to the Washington DC display in 1996, etc.), plus their quarterly newsletter, related links, and much more.

* Marty Howard's HIV/AIDS Home Page
- This is a great page for information and a long list of HIV/AIDS related links. You can also auto-subscribe to many HIV/AIDS related mailing lists through this page.

* Yahoo - AIDS & HIV
- Search Yahoo's links to HIV & AIDS information.

* AIDS & HIV - Information & Resources
- IRCAM in France. Has links in both French and English.

* NIAID AIDS gopher
- The National Institute of Allergy and Infectious Disease gopher.

* TB/HIV Research Laboratory
- Dedicated to research into prevention and treatment of TB and HIV.

* HIVNET/GENA Information Server
- HIVNET and GENA information on AIDS.

* AIDS Patent Project
- Information on AIDS related patents.

* The Safer Sex Page
- The Safer Sex page has info on how to protect yourself.

* CDC home page
- The Center for Disease Control and Prevention's home page, which includes the MMW Report.

* The Joint United Nations Programme on AIDS (UNAIDS)
- "As the main advocate for global action on HIV/AIDS, UNAIDS leads, strengthens and supports an expanded response aimed at preventing the transmission of HIV, providing care and support, reducing the vulnerability of individuals and communities to HIV/AIDS, and alleviating the impact of the epidemic."

- (moderated)

* AIDS NOW! Project for Teens
- Quiz using internet resources to help teens understand AIDS.

* AIDS and HIV (Diseases)
- EINet Galaxy's AIDS/HIV page.

* AIDS Treatment Data Network
- Information about treatments for HIV and AIDS.

* AIDS/HIV Information from the QRD
- The Queer Resources Directory is a good source of AIDS/HIV related info.

* Project Open Hand
- Group that provides nutrition services to people with symptomatic HIV and AIDS in the San Francisco area.

* Rural Prevention Center
- Joint project of Indiana University and Purdue University for the study and promotion of HIV/STD prevention.

*The Biology of AIDS: Compiled Resources
- List of addresses, etc. relating to AIDS research.

* Sida, en Mexico - AIDS in Mexico
- Links of resources. In both Spanish and English.

* HIV Database
- HIV Sequence Database... for the medically minded.

* 1996 International AIDS Conference
- XI International Conference on AIDS information.

- Online version of HIV: An Electronic Information Review. Contains info on HIV treatments and scientific advances.

* HIV Magazines, Periodicals, & E-journals
- Australian and international magazines, etc. (from HIV-EWIR)

- The Center for AIDS Prevention Studies at the University of California, San Francisco. CAPS conducts epidemiological and behavioral studies in the primary prevention and early intervention of HIV disease.

* Keep Hope Alive
- Keep Hope Alive is a comprehensive source of information on nutritional, bio-oxidative and alternative therapies for the immune compromised.

- Pets are Loving Support (PALS) is a service that focuses on helping people with AIDS take care of their pets.

* Condom Sense
- Discount condom distribution site that has a good list AIDS/HIV/STD web links, plus many other features.

* HIV/AIDS Outreach Project
- This site has resource information from the Vanderbilt University Medical Center, a list of online AIDS/HIV Resources, and more.

* AVERT Home Page
- U.K. non-governmental organization that has AIDS information for children and adults, statistics for UK and worldwide, plus other information relating to HIV/AIDS.

* PediAIDS Electronic News Network Home Page
- A volunteer nonprofit pediatric AIDS organization based in Boston, Mass, USA. It's made up of doctors, artists, nurses, social workers, clergy, and anyone who "share an concern for children, adolescents and families living with or at risk of HIV/AIDS."

- Italian AIDS Forum. In Italian.

* Viaticus, Inc.
- Provides financial resources to people living with AIDS, cancer and other life threatening illnesses.

* The Caregivers Guide
- Those caring for those with HIV (or any terminal illness) might be interested in reading The Caregivers Guide by Elizabeth R. Denniston, who wrote it at the urging of her HIV+ son Bruce, while she was caring for him during his illness.

* Releases
- Features poetry and prose written by people with the HIV virus. This site is very well done, and has some very powerful writings.

* Australian Federation of AIDS Organisations
- AFAO represents the main community-based organisations from all states and territories of Australia at the federal level.

* Today's Caregiver Magazine
- "The Magazine for People Caring for Loved Ones." Today's Caregiver is a quartly magazine made by and for caregivers.

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