Hot Topic :: When to start HIV Meds?

The first effective combination treatments for HIV became widely available about 10 years ago. Since that time, ideas about the best way to manage HIV infection have continued to change. I recently spoke with Dr. Calvin Cohen, Research Director of the Community Research Initiative of New England, about how the guidelines for starting treatment have evolved during the past decade, and the different factors that have led to these changes.

Question: Ten years ago, most people advocated a "hit-hard, hit-early" approach for fighting HIV. What were the reasons for adopting that strategy?

CC: Before answering that question, I think it's important to talk briefly about what things were like in the years before HAART - highly active antiretroviral therapy - became available. Until late 1995, there were just four approved drugs to fight HIV, and these were all from the same drug class. These four meds were not strong enough to provide lasting control of HIV and prevent its damage to the immune system. In the days before effective treatment, most HIV-infected persons eventually developed serious illnesses, and many died.

Then, in a relatively few months, the FDA approved five more HIV meds, including the first protease inhibitors (PIs) and non-nucleosides (non-nukes). Around this time, researchers also found that some combinations of three or more meds from different drug classes allowed us to "hit hard," meaning to drive the viral load to very low ("undetectable") levels.

This gave us the ability to reverse the damage to the immune system and thereby reduce the rates of serious illness and death. These very promising findings quickly led to the "hit-hard, hit-early" strategy. The basic idea was that, since the HIV virus was the problem, we should hit it hard with multiple drugs as soon as possible.
The early treatment guidelines reflected this thinking: The general recommendation was that anyone with HIV-related symptoms, a CD4 T-cell count below 500, or a viral load above 10,000 should start HIV treatment.

Question: By the late 1990s, many people were having second thoughts about the hit-hard, hit-early approach. Why was that?

CC: As we gained experience with HAART, our thinking changed for several reasons. We found that many people had difficulty taking their HIV meds consistently, especially when their regimens involved taking many pills several times a day. Poor adherence can quickly lead to drug resistance. When resistance develops, the meds a person is taking may no longer work - and similar meds may also lose their effectiveness. In addition, we found that the HIV meds sometimes caused unpleasant side effects and could lead to other problems, such as increases in blood fat levels and loss or gain of body fat.

In addition, researchers weren't sure whether the meds could maintain their effectiveness for many years. Some felt that, if the benefits of meds lasted only a few years, it might be wise to delay treatment until the meds were needed most. A related concern was that there were still relatively few available meds to fight HIV. If a person's first drug regimen stopped working, then they might have few other treatment options.

These concerns led researchers to question whether HIV-infected persons really needed to start treatment early, or whether it might better to wait. A number of studies have explored this question during the past 10 years.

Question: What have these studies shown, and how has this led to changes in the treatment guidelines?

CC: A number of studies in the late 1990s and early 2000s showed that people generally responded very well to HIV treatment even if they started meds at somewhat lower T-cell counts and higher viral loads. Based on these findings, the treatment guidelines were revised in 2001 to recommend starting treatment when a person's T-cell count dropped below 350 or their viral load rose above 30,000.

Some later studies indicated that it might be OK to wait even longer before starting treatment - at T-cell counts between 200 and 350 and higher viral loads. This led to further changes in the way HIV was treated.

Most recently, however, a major treatment study called SMART found that there may be health benefits to starting treatment when T-cell counts are closer to 350, rather than waiting until counts fall to lower levels. These findings and several other factors have prompted some doctors and patients to consider starting treatment earlier.

Question: What are those other factors?

CC: Well, we now know that the benefits of HIV meds don't always run out, as we had once feared. When taken properly, HIV meds can maintain their effectiveness for many years, perhaps decades. We also have a better understanding of the short- and long-term side effects of HIV meds and how to manage the virus.

In addition, the number of available HIV meds has increased from nine in mid-1996 to 20 today, plus several pills that combine more than one drug. So if drug resistance develops, we have many more backup treatment options than were available a decade ago. Many of the newer HIV meds also require far fewer pills and doses and have fewer and milder side effects than earlier meds. This has made it easier for people to stick with HIV treatment over the long haul.

In the years ahead, we'll continue to review the question of when it is best to start HIV treatment. The answer to this important question will likely continue to evolve as we learn more about HIV, develop more medications, and evaluate new strategies for controlling the virus.

Eric Brus
AIDS Action Committee
294 Washington Street, 5th Floor
Boston, MA 02108
Tel: (617) 450-1432 or (866) 799-0079 (toll-free in Massachusetts)
Fax: (617) 437-6445
e-mail: [email protected]
Web address for more HIV health information: www.aac.org/health

This article was originally published in Forward Living, a monthly publication of the AIDS Action Committee and the Community Research Initiative of New England.