Can HIV Be Eradicated

Protease Inhibitors

Can HIV Be "Eradicated" From The Infected Individual?
June 28

By Jules Levin, Executive Director of NATAP

On June 12 and 13, a well-known group of AIDS researchers were gathered in a two day closed session, sponsored by the peer-review journal Antiviral Therapy and the University of Amsterdam to discuss the questions--can we "Eradicate HIV from an infected individual? And, do we now have the tools to turn HIV into a chronic and manageable disease?

Immediately following the 2-day meeting a telephone press conference was held by a representative group of researchers who participated in the 2-day discussion (Doug Richman, MD, of the University of California-San Diego; Joep Lange, MD-PhD, of the University of Amsterdam; and Julio Montaner, MD, of the Univ. of British Columbia; Luc Perrin, MD, head of the Central Laboratory at Geneva University Hospital).

Following this introduction is a transcription of the press conference. The HIV community should be aware of the proceedings, but it is important to place the discussion in perspective.

Introduction
It is important to note that these discussions are preliminary. We are addressing a theoretical question--can we "eradicate" HIV from the infected person?-- properly designed studies can begin to address the question.

It is pre-mature to as yet accept the notion that we can "eradicate" HIV or are about to turn HIV into a chronic manageable disease. These early suggestions of that are based on an incomplete and small body of research. Some of the studies referred to below upon which this notion is based are small uncontrolled pilot studies, about whose study designs I have some questions. The results are promising, but further studies need to be properly designed and implemented before we place too much stock in them. Confirmation of these theories can only come from a variety of comprehensive additional trials that need to explore a number of related issues, many of which are outlined below.

The researchers discuss below how individuals in the studies to which they are referring, who've achieved viral RNA suppression below levels of detection, are not developing resistance nor progressing. These researchers don't mention in these talks, that for all the individuals who can suppress viral RNA to below detection with a potent therapy, there will be some who may not be able to a suppress their viral RNA below detection; what are the treatment strategies for these individuals? What about those individuals who remain undetectable for a period of time and then their RNA rebounds? What about those individuals who cannot tolerate a 3-drug combination? What about individuals with liver impairment that may have difficulty tolerate drugs that are metabolized through the liver? None of the drug companies, the NIH nor the academic research establishment are even considering researching this latter concern about individuals with liver impairment.

Of course, even the researchers admit that unless an individual is completely compliant with the drug regimens, the chances for success are minimized. Successful protease inhibitor therapy requires compliance---not missing doses, no drug holidays, not taking reduced doses, following the eating and hydration guidelines for the particular inhibitor you may be taking, being mindful of potential drug interactions. Taking a combination therapy of a protease inhibitor (or 2) plus other drug(s) requires even more guidelines to follow. We know that for the collective HIV+ population, compliance is and will be a formidable challenge. Both doctors and people taking these medications are responsible for educating themselves on procedures for proper compliance, and, it is the responsibility of our community, the government, public health officials and the medical community to collaboratively devise a public health program for addressing non-compliance.

HIV may be present in many "compartments" in the body besides the blood. The virus can be present in lymph nodes and other organs. After rendering HIV "undetectable" in plasma, we still do not know the effect on the viral load in these "compartments." Will this hidden virus emerge and be killed by the drug therapy? Can the hidden virus be driven from these "compartments" by the therapy we now have available? Or, will viral replication continue in these hidden "compartments?" Further research is needed to answer these questions.

For individuals with extensive previous drug experience, it is vital to have a timely continuing supply of new drugs. Soon, many individuals will have been on Crixivan or Norvir for 1 or even 2 years; some of these individuals have begun to develop or already have resistance to these drugs, or for other reasons couldn't tolerate them; these individuals will have to transition into untried drugs. Three important drugs are in the pipeline---nelfinavir (Agouron's protease inhibitor), 1592U89 (a potent reverse transcriptase inhibitor showing early impressive data, which may be effective against AZT resistant virus) and 141W94 (VX-478), which is a protease inhibitor; both 1592 and 141W94 are being developed by Glaxo Wellcome. Nelfinavir is currently in phase III trials--and is expected to be reviewed by the FDA by January of 1997. 1592 and VX-478 are in an earlier stage--1592 in phase II, VX-478 in phase I/II. It is vital to our community that the FDA and the developers of these drugs collaborate closely to get these drugs out as quickly as possible. The FDA and Merck and Abbott were relatively punctual with Crixivan and Norvir, but our community placed much pressure on them. We can't afford any slower of a process for these 3 important drugs.

We must continue to devote adequate resources to researching the restoration of the immune system. The prospect of restoring the immune system holds forth much promise. For individuals whose immune system may be depleted, we may need a restorative capacity. The use of immune-based therapies may be less expensive, easier to use and therefore more accessible. The prospects of combining immune restorative therapy with antiviral therapy are promising. We must continue to develop and better support our basic science research initiatives at the NIH, with the goal of better understanding the immune system and its relationship to the virus.

On a more positive note, we are in fact entering a new era for the treatment of HIV because of the development of new drugs and the availability of viral load testing to measure their activity. Never before have we been able to ask the questions--can we "eradicate HIV or make it a chronic manageable disease. But, it is important to be circumspect, to encourage continuing research to address the unanswered questions, and not to allow ourselves to be complacent. The federal government, the drug companies and the academic researchers should be held accountable for properly conducting this research. They must devote adequate resources to the research that we need, and we must keep the pressure on them to do this. To encourage this we do not need unrealistic rhetoric from the drug companies and the press.

Hopefully, I've adequately covered many of the reasons to be discerning when reading these proceedings (although, I may have missed a few), because it is easy to get excited about the promises of the discussions below while overlooking the obstacles.

Proceedings
Dr. Richman said at the outset there is "absolutely no evidence yet that in fact it is possible, but what prompted the meeting was the concordance of data generated in the last 6 months from a number of places to indicate that in various patient populations infected with HIV, antiviral chemotherapy can suppress levels of virus replication to below any levels that can be detected by various methodologies that we have including culture of the virus, measure of HIV RNA and so on. And, that this level suppression eliminates any evidence of resistance and has been maintained for as long as a year or two. These data have been generated in newborns, in adults with primary or new infection, and in a number of adult patient populations with established infection, with several potent combination regimens. It is this encouraging data that has led to this conference to discuss the implications of this in terms of the pathogenesis of infection, the prospects for treatment of patients, how to design future studies to assess the best ways to use these regimens, and what the implications are for the immune system."

Although, Dr. Richman stated that there is absolutely no evidence yet that HIV can be eradicated, the tone of the entire press conference was that a "new paradigm" for treatment of HIV has been established. Properly designed studies must first be conducted to confirm these early findings upon which these assertions are based. Good science should dictate.

Dr. Richman went on to say "the approach of the first decade to antiviral therapy was using available drugs which were only partially suppressive and providing palliation, i.e. just delaying disease. What we're talking about now is a brand "new paradigm" (model) of infection which is to completely suppress virus replication; the alternative outcomes of that complete suppression is either a long-term or indefinite management of the patient with chemotherapy, so that they are turned into a long-term non-progressor or optimistically and this needs to be tested--if patients are suppressed long enough will the last embers of virus be extinguished so that in fact the infection is cured?--we don't know if it can or not, but it's a testable hypothesis."

Individual responses to therapy can be variable. There is the prospect that some individual's viral RNA may not be reduced below detection and others' RNA levels may rise rebound sooner than for other individuals. After this development, how many additional treatment options will these individuals have remaining?

He said the experts at the conference thought that the best time to treat the infection was "early and hard."

A reporter asked-- how easy is it to find individuals in the earliest stages of HIV disease, since most present themselves for testing to discover their HIV status later in their disease progression?

Dr. Montaner said-- ."...we encourage all people infected with HIV to come forward for treatment."

Dr. Richman--"the best data or the highest likelihood of success is in patients experiencing primary or new infection, whether they are adults or neonates. Once an infection is established, what is becoming increasingly appreciated is that a measurement of the plasma HIV RNA can predict those people who are most likely to progress and identify people at risk even when they have very high CD4--there was a paper published in the last couple of weeks in Science (see paper on VIRAL LOAD: Important information) and there's going to be one published shortly in JAMA (Jnl. of American Medical Assoc.). The real issue is how early, and I think most people based on the immunological data that were discussed are also concerned about the prospect of progressive loss or deletion of immune function over time, even in patients who are asymptomatic, which is another argument for early intervention."

Dr. Montaner--."......we would prefer to treat people earlier when they have a relatively lower amount of virus band viral load is relatively low, because that's where we're getting the highest likelihood of success; the immune system is preserved, you don't have to restore anything, you're basically preventing things from happening. Even for individuals with low CD4 counts, in the 300 range or even lower, they can have a very good response--80% (reference to the Boehringer Ingelheim 1046 study of drug-naive of AZT/ddI/nevirapine--see Nevirapine article) or more of them becoming viral load negative in plasma or undetectable, when treated with the more aggressive regimens. That is very encouraging and leaves it open for everybody to approach treatment in the same way with the aim to make viral load undetectable or as low as possible for as long as possible."

The nevirapine trial and those in sero-converters and drug-naive individuals all study individuals who are the most likely to benefit from treatment because they've never used treatment before; what about the large population who are very drug-experienced, how will they respond? Throughout the entire talks here, very little discussion if any at all is devoted to this group of individuals. People with advanced HIV cannot be written off; effective research strategies must be devised for them.

Dr. Perrin--"Another issue is that of tolerance; the later one starts treatment the more problem one may have with tolerance.

Dr. Montaner-- "Also potential drug interactions, some of the drugs that we're talking about may have substantial drug interactions that may compromise their use with some of the medications that are necessary in the advanced stages of the disease. The rational for treating early and aggressively is very solid."

Reporter-- I recently spoke to a number of physicians, AIDS specialists from around the country and the majority are very conservative in their treatment and did not feel that they wanted to go heavy and hard at an early stage; they might use nucleoside analogues first and try and save the protease inhibitors until later; a lot of their thinking is you don't want to use all of the arrows in your quiver.

Dr. Montaner--"They're using the wrong approach; unfortunately, this is nobody's fault; we didn't know any better. Let me give you an example of some of the data that we presented here. We looked at a combination therapy study looking at combinations of AZT+ddI or AZT+nevirapine or AZT+ddI+nevirapine, this data is now in the public domain, as it was part of the package presented to the FDA for approval of nevirapine; what we were able to show with nevirapine, which is a drug for which resistance develops very rapidly when used alone, sequentially or as an add-on to previously treated individuals--what we were able to show is that by introducing treatment with 3 drugs at once you are able to prevent the development of drug failure, presumably drug resistance, because almost all the patients who were able to tolerate the medication became non-detectable in plasma viral load. The message coming out of the studies discussed here, but in particular this study because of the uniqueness of nevirapine in terms of its ability to generate resistance, confirms the notion, in my view, that if you hit hard and early and if you suppress viral replication as we can measure it today, that you virtually can expect that the treatments will remain effective for a prolonged period of time. Don't ask me for how long, because the study is ongoing but we data now up to 18 months, but we see now people on this regimen who remain plasma viral load negative for very prolonged periods of time, as we haven't seen before.

Dr. Richman--"One of the reasons for the conservative approach that you described is that, that has been the practice and all of the data we've been talking about in this meeting are unpublished, in fact almost none of the studies are even submitted yet for publication. But, the confluence of the data plus everything we've learned over the decades about chemotherapy of tuberculosis and oncology is that using the drugs for such large complicated biologic populations has to be done early, hard and in combination, rather than in sequential steps. The thinking will be changing but this is sort of the beginning of that.

Dr. Montaner--"At the Vancouver conference, I think you will see a convergence of a large number of studies, both natural history studies and clinical trials, which are basically going to clarify this issue in the minds of most treaters. The message coming out of this scientific program is very consistent throughout, that this basically is the approach which offers the best chance of maintaining the ability of these drugs to remain effective for prolonged periods of time. Very soon, over the summer, we will see the change in attitude of the treaters based on a large body of evidence."

Reporter-- The only drug names I've heard so far are AZT, ddI and nevirapine. Are you talking about treating early on from the start with a combination that includes one or two protease inhibitors, could you be specific in how you would use protease inhibitors.

Dr. Richman--"The data include the use of nucleosides and protease inhibitors. The data that Dr. Montaner presented yesterday were the first to show a potent combination of nucleosides with the combination of a non-nucleoside reverse transcriptase inhibitor. Which combinations, how they'll be used, whether 4 drugs will be combined, whether there will be an induction with a very potent regimen followed by maintenance with a less complicated regimen---these are all issues that are now going to have to be addressed when we go back to work.....as we get more drugs, there are more combinations and permutations that can be generated and which are the most potent, the least toxic and the least expensive will be the ones that people will pursue. But, because of the issue of prior drug history in a number of patients, having alternatives provides alternative potent combinations for people in different situations.

Dr. Montaner--"To summarize the approach I would like to take with my patients, if I had all the options available: --to offer individuals a regimen that is available, --relatively well-tolerated, --with a low likelihood of drug interactions or side effects, --that is anticipated to bring down viral load to a level of non-detection in that individual.

"We are learning for the first time that there are several approaches that can be taken. Data has been shown, for example, for AZT/3TC/indinavir--AZT/ddI/nevirapine and a number of other combinations that will present options for patients.

"We have put a face to the enemy--we can target our therapy, we can look for it, where it's at and where we want to drive it.

"The treatment of HIV is now entering a stage where it becomes a dynamic process. You have a number of options; you have an understanding of what the drugs can do. The availability of viral load measurement of drug activity affords treaters with the capacity to within a few weeks to detect the results of the initiation of therapy and with the ability to follow its path."

Reporter--What was the longest period of follow-up with protease inhibitors, that was presented at this meeting?

Dr. Richman--"Complete suppression in patients has been observed for up to two years in patients on various regimens. The phenomenon of complete suppression occurs in --the proportion of people who experience complete suppression is a function (1) of the potency of the drug regimen, (2) starting level at which they are treated and (3) compliance of the patient to the regimen. The small number of patients in these studies who are most likely to fail are those who don't adhere to the regimen for whatever reason. The biologic principle is that drug resistance can't develop if virus can't replicate. So, once we've suppressed virus sufficiently resistance doesn't emerge and suppression is sustained as long as the patient takes the drug.

Dr. Montaner--."......if you prevent viral replication, you won't get resistance. That truly changes how we approach to the disease and treatment."

Reporter-- What exactly do you mean by reducing the level to undetectable, does that mean that level is low enough so the person is no longer infectious?

Dr. Richman--"The most sensitive readily available assay now is the Roche RT-PCR assay and that can be read down to 100 to 200 copies/ml of plasma. With some modifications we can assay by PCR down to 10 or so copies/ml of plasma; these patients we're talking about are below that threshold. In addition, patients have culture positive plasma and peripheral blood mononuclear cells (PBMC) almost invariably, and that has been cleared in all these patients; that is what we mean by undetectable. Early on, after they are rendered undetectable one can still detect remnants of virus in the lymph nodes, but the question is can we drive these levels below detection at some point, and that remains to be determined. What we do know is that there is not enough replication ongoing at low levels for resistance to emerge. The question is whether the infectious process will ultimately be extinguished.

Dr. Montaner--."....we don't know if a patient who is undetectable and remains undetectable for a period of time becomes less infectious. Studies need to be conducted......some of the assumptions are that virus is located in mostly compartments or cells that are going to die off over a relatively short period of time, but you could similarly argue by assuming they are remnants of cell populations that have long half-lifes that remain infected and provide a reservoir of virus that will oblige us to maintain treatment for a long period of time. And, this all has to be tempered by one key issue-- ability of patients to take the treatments that we're proposing; this challenge should not be underestimated. Tuberculosis is a treatable disease with a relatively shorter term of therapy, but for the fact that compliance with taking the prescribed medications is not easy.

"The controlled and randomized trial of AZT/ddI/nevirapine studied 151 drug-naive individuals with CD4 between 200-600 CD4. For the patients randomized to this 3-drug therapy, nearly 80% of the patients, on an intent-to-treat analysis, were able to maintain an undetectable viral load. Upon further analysis, they found that all but one of the patients taking the 3-drug therapy who were able to comply with the regimen had complete suppression of plasma viremia as indicated (for more details, see Nevirapine article)."

Reporter--I'm not hearing anything new. It sounds like what I heard at the Retrovirus meeting in January with some minor updates, so what's the news?

Dr. Richman--" Nothing regarding complete suppression has been published or, to my knowledge, even accepted for publication. You're right, at the first presentation at the Retrovirus meeting caused a big splash. What we saw here at this meeting was significant extensions of the data with different patient populations including neonates, primary HIV infection, different regimens and discussions with mathematical biologists about modeling study designs and eradication. Dr. Perelson showed the first data regarding the second phase of decay of a different infected cell population. The practical issues of how to take this information and design studies and patient management strategies."....were discussed.... "you're right it's not an unprecedented observation but a lot of additional information was presented and discussed.

Dr. Perrin--"Several groups have patients who have been with undetectable viremia for more than 1 year; people are asking themselves what should we do? Should we continue the same way with the same regimen, should we add other regimens, should we stop therapy.......this is a scientific question......everybody is interested and nobody knows what is the answer."

Reporter--What do we have to do to get the level of deductibility in PCR down low enough so that we have some greater degree of confidence about the interpretation of the so-called no-detectable level? --and-- What are we going to do to make this "eradication therapy", if we want to use that word, affordable?

Dr. Richman--"There are laboratory methodologies to get down to 10 copies (RNA) or lower, but some of these lab investigations will require things like lymph node biopsies, which are being done on these patients, and preliminary results are just beginning to come along, and that's an important part of figuring out what's going on. In the long run, additional generation assays whose threshold is lower than the 100 copies will be desirable. In terms of cost, the hope is that the more drugs we have, there will be additional cuts. The fact that Merck undercut the other protease inhibitors for price was positive for all protease inhibitors and all subsequent drugs that come along. Hopefully, the more competition there is in the field, the lower the cost will be.

Dr. Perrin--"If 'eradication' is possible, in the end it will be cheaper even if you have to use 4 drugs; if you use them for 4 years and you're cured its going to be much cheaper than what we're doing now."

Dr. Richman--"There are two reasons for potential optimism, the most optimistic situation would be 'eradication' which would eliminate all subsequent costs once it was instituted. The second is the prospect of the oncologic model where you have induction followed by consolidation or maintenance regimen, so that the complex combinations would be used for a shorter period and then long term management would be with maintenance suppression. Both of these prospects are theoretical, but we can now actually ask the questions and design the studies to investigate them."

Reporter-- Given that you can bring down viral load to low levels or not having replication at all, the cells that are infected are still alive, how do you go after them?

Dr. Perrin--"That's one of the crucial issues. The cells that are chronically infected and that you don't get to with your drugs, do they die at a certain stage and how long does it take? How long is the half-life. That will determine how long you will have to continue your therapy. There are optimistic and pessimistic predictions."

Dr. Montaner--."..Dr. Ho and Dr. Shaw presented evidence that 99% of the virus are produced by actively or positively infected CD4 cells. The half-life of these cells is around two days. Other cells that are infected, for example macrophages--whose half-life we are not sure of; it is the half-life of these cells that will determine the amount of time we'll have to treat patients."

Reporter-- Does this mean that you feel there's a possibility that the suppressive drugs alone are enough to achieve eradication, or do you need to couple that with immuno-therapy to go and get that last 1% of long-lived cells?"

Dr. Richman--"If HIV is like Herpes, we'll never be able to 'eradicate' the infection. In other words, Herpes infects a type of cell that is life-long, so that we can only suppress Herpes we can't eradicate it. HIV may fall into that category but it may not; and, if it doesn't then its just a matter of potency and duration of therapy. Basically, we're designing experiments to address that."

Dr. Montaner-- "For the first time we have the ability to reliably suppress viral replication and your question opens the door for speculation, but all we can say with confidence is that we will continue to watch and monitor these people closely to see what we learn, in terms of to what extent we are able to "eradicate" the virus. Are we bringing it down or is it disappearing, we cannot answer this today."

Reporter-- Many studies that have come out over the past few years, for example on AZT which seemed to indicate that the drug had very little value and prompted many patients to not only get off the bandwagon but to denounce the drug as an evil, you're saying that was way pre-mature?"

Dr. Richman--"It's analogous to cancer chemotherapy or TB, where any drugs which only had limited activity for a short period of time on their own, are very useful or critical components of combination regimens. It was a big mistake to write off the old drugs.....it was pre-mature and destructive; it was a study design that asked a question which was at that time even obsolete because ddI and ddC were available and the message that it delivered was very destructive to clinical management, public health and drug development."

Reporter--"So you're saying all those studies were flawed, the Concord study and others that reached those conclusions?"

Dr. Perrin--"At the time the Concord study started, we knew that monotherapy wasn't going to do the job."

Dr. Montaner--.".....if you were hoping that one single drug was going to do it, that was wrong. Obviously, we have now proven that was not the right approach. What we're saying is that drugs that cannot do it alone, certainly can do it when you combine them appropriately; and AZT alone cannot do it but if you combine it with another drug or two.....you can arrive at complete viral replication and maintain that for a prolonged period of time."

Reporter--"When the time stars to run out for a particular regimen for a person then would you switch them to another combination to keep it going for another 3 years?"

Dr. Montaner--"We now have people that are responders to particular regimens of combination therapy, for whom we cannot detect active viral replication and we have no reason to believe that these people are going to fail on that particular combination in the foreseeable future. I cannot rule out the possibility that people can find their combination that works for them and they can remain on that combination for a very prolonged period of time."

Dr. Richman--"The small subset of patients who have been called long-term non-progressors have low but measurable levels of viral RNA and usually can have virus cultured from their PBMC (Peripheral Blood Mononuclear Cells). We are driving the levels of virus lower than that, so the consequence of being able to suppress virus to these low levels turn patients into long-term non-progressors; so that, if this results in "eradication" and cure that's wonderful; if it doesn't, then we will be talking about managing patients on a chronic basis analogous to hypertension or diabetes... there are two differences between long-term non-progressors and this group; to maintain their viral suppression they have to take drugs......and secondly, when we are treating these patients, they've already sustained some immunological destruction which the long-term non-progressors haven't. How much can be restored when you intervene late is another question that is now able to be investigated properly."

Dr. Montaner--"The data suggests that long-term non-progressors will show evidence of progression in the long run."

Reporter--"I have not heard you mention the word mortality. It's nice that you can suppress viral load to low levels but the real question is are patients living longer?"

Dr. Perrin--.".......there is enough data now that show that suppression of viral replication is buying them survival time."

Reporter--"How much more time?"

Dr. Richman--"You can't do an experiment for a year and say what's going to happen in 20 years. We're at an early stage in this. If we can sustain it (viral replication) there is no reason to believe HIV will result in the immuno suppression that will kill patients."

Reporter--"But as far mortality data, you don't have....."

Dr. Perrin--"We have retrospective studies......he looks at the predictive value of viral load......Mellors has found that patients with less than 5,000 copies........they survive longer than patients with higher viremia. By analogy, we are saying if we can push down viremia in patients for a long time it prolongs their survival time."

Dr. Richman--" Dr. Katzenstein showed data from ACTG 175, which was just combinations of AZT, ddi and ddC, that the clinical benefit including mortality benefit of antiviral therapy could be almost completely explained on the basis of the amount of reduction of RNA that was achieved even with those what we now consider limited regimens. With complete suppression, we have seen no progression of patients who've been on these regimens, but there limited numbers and limited periods of time."

Dr. Montaner--.".......in the context of anti-retroviral therapy, we feel confident that, with the use of drugs we are taking about--protease inhibitors, nucleosides, non-nucleosides--the value of dropping the viral load through therapeutic manipulation has now been validated. The data that Dr. Richman is referring to, which is coming not just from 1 study, but from several studies, indicates that the mechanism through which these drugs have an effect on viral replication can be measured by measuring viral load......what is the survival advantage of using three drugs at once and making your viral load negative? The answer can only be speculative at this time because we haven't followed these individuals long enough; but, what we can tell you is that we feel very confident on the basis of the data that we have that this represents a substantial improvement over what we had before; and, if we now have the data that shows that AZT/ddI improves survival over AZT and AZT over no treatment, there is an incremental gain in our opinion by going forward with aggressive strategies to suppress viral replication."

Dr. Richman--."......what has been observed anecdotally is that some of these patients who have had chronic opportunistic complications like KS or cryptosporidia diarrhea have anecdotally shown some remarkable improvements with the restoration of their CD4 cell counts; but, those are anecdotal and systematic studies to address these are now being designed......as well a research program at Duke University was described at this meeting to look at the ability of thymic transplantation to accelerate immune restoration in these patients, but their initial experience presented was for children with congenital immuno-deficiency and described what they plan to do with HIV patients; there is no data yet but its a study that's in progress."

Reporter--"If you say the evidence indicates to "hit hard and early", how early is early? And, should HIV testing become a routine part of everyone's annual check-up?"

Dr. Richman--"The most promising effects are seen in primary infection in adults and neo-nates, from everything we know about chemotherapy...........early is best.....everybody should be tested for HIV sero-status and all people who are positive should have their RNA levels ascertained to determine their risk of progression."

Continuing research is necessary. We cannot become complacent. The theories discussed above must be confirmed with properly designed studies. Basic science research at the NIH must continue to receive proper support and development towards the possibility of discovering restorative therapies for the immune system. A public health menace of non-compliance must receive adequate attention. Good science should dictate.

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About the author: Jules Levin is the Executive Director of NATAP, based in New York City.

The National AIDS Treatment Advocacy Project (NATAP) is a New York State non-profit corporation dedicated to facilitating the effort for development of effective treatment for HIV.

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