TREATMENT REVIEW 32 - 33 - Fall/Winter 2000

In previous issues of Treatment Review, we have reported on some exciting new research into the immune system. The goal of this research is to try and get the immune system to a better job of controlling HIV replication. It's been known for a long time that some people with HIV do not progress to AIDS or get sick. In these people, T4 (also known as CD4) cell counts stay normal and the viral load stays low or undetectable without any treatment. Individuals in this group are called long-term non- progressors (LTNPs). Studies have found that only about 1-5% of people with HIV are LTNPs.

As we reported previously, researchers have now found immune system responses against HIV that seem to be unique to LTNPs. One researcher, Bruce Walker of Harvard University, has been at the forefront of this research. His studies showed that LTNPs have large numbers of T4 helper cells that are actively fighting HIV. These T4 helper cells work alongside another type of T-cell called a T8 cytotoxic T-lymphocyte (or CTL for short). When T4 helper cells send the proper signal, CTLs can target and kill HIV-infected cells in the body. Walker found that LTNPs also had CTLs that were actively hunting down and eliminating HIV-infected cells.

In people that aren't LTNPs - the majority of people with HIV - Bruce Walker has found that there aren't large numbers of T4 helper cells fighting HIV. There are usually CTLs, but without the T4 helper cells to send them the right signal, the CTLs don't do a good job of killing HIV- infected cells.

Dr. Walker and other researchers are now trying to stimulate the immune system to produce T4 helper cells that can fight HIV. We reported on some of Walker's early study results in Treatment Reviews #29 & 31. More information from this and several other studies has since been presented.

Dr. Walker's study began by treating people very soon after they became HIV-infected. People in this study were treated with combinations of anti-HIV drugs (Highly Active Anti-Retroviral Therapy or HAART). After a year or so of treatment, Walker found that these individuals had T4 cells and CTLs that were fighting HIV. To see how well these HIV-fighting (researchers describe them as HIV-specific) T4 and CTL cells could control HIV, people in Walker's study have begun to take breaks from their HAART drugs.

In a recent issue of a scientific journal called Nature, Dr. Walker and his team reported on eight people from this study who have stopped HAART. All eight had started HAART treatment no longer than 180 days (about six months) after becoming HIV-infected. The length of time on HAART before stopping was 1-3 years. The study was set up so that people would restart HAART if their viral load increased to over 50,000 copies, or if their viral load increased to over 5,000 copies for more than three weeks.

After stopping HAART for the first time, all eight people had an increase in viral load. However, three individuals saw their viral loads drop to less than 5,000 copies without restarting drugs. Two have now been off HAART for over seven months and have viral loads less than 500 copies. The other person restarted HAART after a three month break although their viral load was still less than 5,000 copies. This individual then stopped HAART a second time and has now been off drugs for over 5 months with a viral load of 280 copies.

The other five people in the study were all required to restart HAART by the researchers, four of them because their viral load increased to over 50,000 copies, and one because their viral load increased to over 5,000 copies for more than three weeks. These five people later stopped HAART a second time. Two have now been off HAART for around six months and have viral loads of less than 500 copies. Another two decided to restart HAART, although they were not required to by the researchers. One had a viral load of 4,600 copies, the other had a viral load of 10,860 copies. The fifth individual's viral load increased to 17,100 copies after about 5 months off HAART and this person met the requirement for having to restart HAART.

In total, five of the eight people in the study have maintained viral loads off less than 500 copies after one or two interruptions in HAART treatment. These five people have now been off HAART for an average of six months.

When the researchers looked at HIV-specific T4 cells and CTLs, they found that stopping HAART seemed to boost the number of these cells. There was also an increase in the number of parts of the virus that the cells were targeting. The boosting of these HIV-fighting cells was linked to better control of HIV viral load when the drugs were stopped. The researchers are continuing the study to see how long the immune control of HIV without HAART lasts. They are also measuring the HIV-specific T4 cell and CTL responses to see if they stay strong over a longer period. At the moment, these study results are very short term and involve only a few people, but Walker's team is very encouraged by what they've seen so far.

The next priority is to see if these HIV-specific immune responses can be boosted in people with longer-term HIV infection. The ultimate goal would strengthen the immune response against HIV enough that HAART could be stopped, if not permanently then at least for extended periods of time. At first, Bruce Walker and other researchers didn't think this would be possible. The exciting news from recent studies is that it does seem possible to boost HIV- specific T4 cells and CTLs in people that have been HIV- infected for a long time. Several studies have now shown that, under certain circumstances, interruptions in treatment can lead to a boost in HIV-specific T4 and CTL cells, even in people that have been HIV-infected for many years. New vaccines that are entering clinical trials may also be able to create HIV-specific T4 and CTL cells when HIV is being controlled by HAART drugs. These are called therapeutic vaccines.

A Word of Caution The Network has been following reports about Dr. Walker's research for several years now. Although the news continues to be very exciting, there is still not enough information to recommend that people on HAART try interrupting their treatment. For people interested in trying these immune-boosting strategies, looking for a clinical trial is the best way of making sure you'll be properly monitored. There are new clinical trials investigating both strategic treatment interruptions and therapeutic vaccines. Call The Network for referrals to these studies. You can also call us and request copies of all the articles on this topic from our Treatment Library - as with all Network services, there's no charge.