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Monday, 23 February 1998

AIDS Treatment News Issue #289

By John S. James



Clinical Implications of Virological "Failure": Interview with Steven Deeks, M.D., San Francisco General Hospital

Retroviruses Conference Notes

Retroviruses Conference: For More Information

Opportunistic Infections: Major New Report

Clinical Implications of Virological "Failure":

Interview with Steven Deeks, M.D.,

San Francisco General Hospital

By John S. James

Recently physicians have noticed that some patients, being treated with a protease-inhibitor-containing regimen which failed to control the virus, still maintained a better CD4 (T-helper) count, and seemed to be doing better clinically, than would have been expected given their viral load. The most extensive report yet on this observation--from a cohort of 143 "virologic failure" patients followed for a median of 18 months at San Francisco General Hospital--was presented as a poster at the 5th Conference on Retroviruses and Opportunistic Infections in Chicago.(1) AIDS TREATMENT NEWS interviewed lead author Steven G. Deeks, M.D. on the findings of this study, and also on the current practices of physicians at San Francisco General Hospital in treating patients whose viral load could not be reduced to undetectable levels by antiretroviral therapy.

Summary of the Poster Presented at the Retroviruses Conference

The study by Deeks and others was a retrospective review of the medical records of a cohort of patients at San Francisco General who met a strict definition of "virologic failure." To be included in this cohort, patients had to (1) have had more than 24 weeks of continuous treatment with regimen containing a protease inhibitor (either indinavir, ritonavir, nelfinavir, or ritonavir plus saquinavir), (2) have had two consecutive viral load measurements of greater than 500 copies/ml (using the branched DNA test) at their last two clinic visits, and (3) have received ongoing care at San Francisco General Hospital. 143 patients met these criteria and were included in the review. Of the 108 who had a viral load test available before starting protease inhibitors, the median baseline viral load was 4.84 logs (about 70,000 copies), and the median baseline CD4 count was 82.

In the entire cohort of 143, followed for a median of 18 months, there were seven deaths: four were not AIDS related, two were from AIDS-related dementia which preceded the protease inhibitor treatment, and one was from invasive aspergillus. In the entire cohort, there were only eight new AIDS-defining events during the followup period: two cases of non-Hodgkin's lymphoma, two pneumocystis, one cryptococcal meningitis, one cutaneous Kaposi's sarcoma, one PML, and one invasive aspergillus. There were no new cases of CMV or MAC.

More analysis was possible on the 108 patients who had a baseline viral load. Before the analysis, the patients were divided into three mutually exclusive groups: (1) Non-responders, with no viral load reduction greater than one log below the baseline (meaning that the antiretroviral regimen never reduced the amount of virus in their blood to a tenth or less of its pre-treatment level); (2) Transient responders, who did have at least one viral load measurement one log below baseline, but whose viral load had returned to within one log of baseline at their last visit; and (3) Durable responders, who had a greater than one log reduction in viral load at their last visit (but who, like all the others, still met the strict "failure" definition of not being below 500 copies on either of their last two visits). By these measures of response, there were 22 non-responders, 45 transient responders, and 41 durable responders (total 108).

At 18 months, even the "non-responders" had a median CD4 count increase of approximately 50. The transient responders had a median CD4 increase of more than 100, and the durable responders had over 150. The median CD4 increase for all 108 of these "virologic failure" patients was approximately 100.

The following conclusions are quoted from the poster:

"Despite a median duration of 18 months since initiating a potent PI-containing [protease inhibitor containing] regimen, and greater than 12 months since the emergence of virologic failure, the median absolute CD4 T-cell level in this cohort remained approximately 100 cells/mm(3) above the pre-PI baseline.

"A significant proportion of patients with an incomplete response to a PI-containing regimen had a durable 1 log or greater decrease in viral load. This durable suppression was associated with a sustained increase in the absolute C4 T-cell count.

"Patients who had a transient virologic response to a PI-containing regimen had also significant and sustained increase in the absolute CD4 T-cell count.

"New AIDS related events were uncommon in this cohort of 143 patients 'failing' a potent PI containing regimen (n=8). There were no new cases of CMV or MAC.

"These observations suggest that failure of a PI-containing regimen, defined virologically, may not be predictive of subsequent CD4 T-cell decline (over the following 12 months).

"These observations must be considered in light of the retrospective nature of this study, and the limited duration of follow-up. Long-term follow-up of this cohort is needed to further examine the clinical implications of PI failure."

The Interview

We asked Dr. Deeks about this study, and about treatment of such patients at San Francisco General Hospital, which is widely recognized as a leader in AIDS care. The interview took place on February 12, 1998.

AIDS TREATMENT NEWS: In this study of clinical consequences of virologic failure of protease inhibitor therapy, why were the "durable responders" counted as treatment failures?

Dr. Deeks: They did not meet the strict criterion that has become the gold standard of therapy, which is to achieve sustained undetectable viral load. They had a clear response; the viral load went down and stayed down, but at least in the last two visits it was detectable (greater than 500 copies/ml using standard bDNA assay).

ATN: In this study, were there predictors of who would do poorly--predictors that might be helpful for clinicians in managing patients?

Dr. Deeks: Our presentation was only meant to report, "This is what we saw." To take this observation and conclude how clinicians should use viral load and CD4 data would be premature.

Our data simply state that the patients we identified as having "failed" protease inhibitor treatment still clearly had a sustained CD4 increase. That is a major point of this presentation. We are not saying that patients will not progress eventually. But as far as we can tell, over the 12 to 18 months after we recorded failure, for the vast majority of patients, CD4 decrease or clinical progression did not occur.

We did have a small group who developed opportunistic infections: only eight in this cohort of 143. What was constant with most of them is that even though they may have had a viral load response to their therapy, they never had a CD4 count response. This was consistent with what Dr. Judy Currier reported in her analysis of ACTG 320;(2) that analysis showed that for patients who received AZT and 3TC, or AZT, 3TC and indinavir, just a small increase in CD4 count above their baseline (after eight weeks of treatment) was highly associated with a good clinical outcome. Our data were consistent with their observations.

One possible take-home message is that if patients do get even a small T-cell response, that may translate into prolonged clinical benefit. Patients who do not see a T-cell response to protease inhibitor therapy might benefit from more aggressive prophylaxis of opportunistic infections.

Yet our results cannot prove that if you fail protease inhibitor therapies virologically then you should stay on that particular regimen--or even that you should necessarily stay on therapy. To answer those questions would require a prospective clinical trial comparing the different options that patients have: stopping therapy, switching therapy, or staying on therapy.

ATN: What are the risks of staying on therapy despite virologic failure?

Dr. Deeks: By allowing viral replication in the face of a selective pressure, high level drug resistance may develop. This process may continue to occur long after the viral load starts to increase. It may limit future options with so-called "salvage therapy" down the line.

A second risk is continued side effects, which for some patients may outweigh any durable benefit from these therapies. And the cost of these drugs will be a factor for some.

In our clinic the vast majority of patients, once they failed the protease inhibitor virologically, either stayed on that therapy or switched to a second protease inhibitor containing regimen. And virologically, those groups basically did about equally well. We have not had many patients achieve durable viral suppression after switching to a second protease inhibitor containing regimen. Whether or not these people would have done as well had they stopped all their drugs, we do not know.

Of note, clinical investigators at Johns Hopkins University have reported reasonable success in patients who switch early to a second protease inhibitor containing regimen.(3) The fact that some of their patients switched early may be critical. Delaying the switch for months, which was common in most of the patients we studied, may allow for the development of high-level resistance.

ATN: Is there any observation from those who did choose to stop everything?

Dr. Deeks: We only had about half a dozen patients who chose to stop antiretrovirals because of virological treatment failure. Among clinicians at San Francisco General Hospital, there is a strong sense that stopping therapy is not a good thing to do. So we do not have data to make a comparison.One possible criticism of our data is that only those patients who did well stayed on therapy. We do not believe this was a significant issue in our analysis, since very few patients stopped therapy--and all patients, including those who stopped, remained in the analysis.

So again, we can only offer the observation that virological failure is not necessarily equal to clinical failure, over 12 to 18 months. But people should not take this and say, "I failed my protease inhibitor, but I should stay on it." We really do not know that, and certainly there are risks instaying on the drugs.

ATN: Have you seen increased viral resistance in these patients?

Dr. Deeks: We have not looked for it yet, and do not have much resistance data on these patients now. We need to do this analysis.

ATN: What research ought to be done next?

Dr. Deeks: The virologists and immunologists need to take a close look at this phenomenon, and try to determine if there is any underlying reason to think that virologic failure and resistance to a protease inhibitor confers loss of virologic virulence. This is a major question clinicians have been asking. There are some small studies suggesting that it may be true. A paper published a few months ago suggested that resistance could result in a switch from a syncytium inducing phenotype (SI) to a non-syncytium inducing phenotype (NSI)(4); this could explain why resistant virus would be less destructive to T-cells. Other observations along those lines would also suggest that resistance to a protease inhibitor comes at some significant cost to the virus. These are the kinds of virologic studies that need to occur. I am told that it is very difficult, however, to test a virus for virulence in the laboratory. We are interested in working on this problem here at the Gladstone Institute [a privately funded nonprofit research facility associated with San Francisco General Hospital].

The other issue is what exactly is happening in the immune system--which goes back to the fundamental question of how HIV causes immune destruction. Is it a direct effect of the virus on the CD4 T-cell, or is it something much more fundamental earlier, a view many investigators are coming to support?

ATN: In other words, not the virus killing the CD4 cells, but doing something that prevents the cells from being produced in the first place?

Dr. Deeks: Yes. And it is possible that the transient virologic response to a protease inhibitor could lead to a sustained immunologic benefit. If the problem caused by the virus occurs early in the development of the mature immune system, one could envision that even a brief period of time when the virus was not around could let the immune system regenerate itself. Therefore immune function could be more sustained in the face of the virus coming back up, and that could lead to a sustained clinical benefit. The implication, however, is that eventually progression will occur. But when that may happen is unknown.

If you look closely at the data from the nucleoside analog trials, the CD4 count response is more sustained than the virologic response. So what we have reported may not be associated with protease inhibitor failure specifically. It may be a phenomenon of antiretroviral drug failure.

ATN: What would we need to answer the question of whether people should stay on treatment, or go off? Would a clinical trial be necessary?

Dr. Deeks: I doubt that people would support such a trial now--taking patients who "have no clear options to switch to" and randomly assigning them to go off all antiretroviral treatment, or to recycle drugs that had not worked for them. My sense has been that many clinicians and patients would not participate in such a study. So we will always have inconclusive data.

What needs to happen for these patients is not to answer the question of stop, or change, or recycle--but to develop new and better drugs.

Caution on Starting NNRTI Drugs After Protease Inhibitor Failure

Dr. Deeks: At San Francisco General Hospital, for our patients who have failed more than one protease inhibitor--and they are very common here--one approach has generally been to keep them on whatever drug combination is best tolerated, and avoid adding or changing to any of the newer drugs, particularly the non-nucleoside reverse transcriptase inhibitors. The goal here is to save these drugs for when we know how best to use them in "salvage" regimens. Until then, the goal of therapy for patients who have failed their first-line therapies is to move from seeking viral suppression, toward seeking sustained clinical benefit. It can be difficult to distinguish between these two. But a strong feeling of physicians here is not to play the non-nucleoside RT inhibitor card for these patients until you have to--that is, until patients are progressing clinically. Perhaps over the next year we will have clinical evidence on how best to approach patients no longer responding virologically to protease inhibitor therapy. Presumably, the non-nucleoside reverse transcriptase inhibitors will be a critical component of that strategy.

ATN: Do you mean efavirenz in particular?

Dr. Deeks: Or nevirapine or delavirdine. These are very potent drugs--but they rarely do much, unless they can be given with two other drugs which will be very effective. And for these patients who have gone through the first line of antiviral therapies, there probably are not one or two other drugs that are going to be effective enough to lead to complete suppression.

Viral Load: How Low Is Low Enough?

ATN: Do you have any thoughts on the issue of whether a viral load below 400 copies is good enough, or do you really want to be below 50, 40, or even less?

Dr. Deeks: This is one of the questions that clinicians are going to struggle with over the next year. The data that Dale Kempf from Abbott Laboratories presented about a year ago clearly shows that the lower you get, the longer you stay down;(5) that makes sense. So the goal of therapy will be to get the viral load as low as possible; the way to measure that would be with one of the new ultrasensitive assays.

The problem is, what do you do when the viral load does not go so low? This is a fundamentally different question. If you get down to very low levels, less than 400 copies, but the virus is still detectable, and it stays at this low level, what do you do then? Do you add drugs? Do you change the entire regimen? Do you continue to follow patients and watch what happens? The problem is that these new tests provide you with powerful information, but we do not know how to use it. So I myself do not see a dramatic need right now for access to the ultrasensitive assays. They will cause more confusion when they become more widely available.

The data from Keith Henry, from his clinic at the University of Minnesota, would suggest that a large proportion of patients who are "undetectable" with the standard assays will be detectable with the ultrasensitive assays.(6) So it will be a real concern.

Some other posters at the Retroviruses meeting are relevant here. One looked at five vs. four vs. three drugs(7); this was a relatively small study done in Europe. Researchers looked at viral decay rates over the first two weeks [how fast the virus decreases when combination antiretroviral treatment is first started], and observed that as you increase the number of drugs the patients begin with, the decay increased substantially. To me this suggested that the three-drug combinations now used, for example the classic AZT plus 3TC plus indinavir, might not be enough to fully suppress viral replication--since if you go to four or five drugs, you get more rapid decline. This would suggest that current three-drug regimens may be suboptimal for some patients, which may be why we see drug failures even in patients who are completely adherent to these regimens.

How important is it to get the viral load to extremely low levels? Obviously the gold standard test for answering this question would be lack of clinical progression. But in people who get to these very low levels, we see very little clinical progression; it would take years to distinguish between those under 400, for example, vs. those under 40. In practice we will never know the answer for sure.

So it comes back to the theory. Theory drives much of what we do, and probably it should. Here theory would suggest that the less viral replication you have, the less resistance you will develop, and the longer these drugs will work. So getting the viral load as low as possible should be a central goal of therapy.


(1) Deeks SG, Beatty G, Cohen PT, Grant R, and Volberding P. Viral load and CD4 + T Cell Changes in Patients Failing Potent Protease Inhibitor Therapy. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #419].

(2) Currier JS, Williams PL, Grimes JM, Squires KS, Fischl MA, and Hammer SM, for the ACTG 320 Study Team. Incidence rates and risk factors for opportunistic infections in a phase III trial comparing indinavir + ZVD + 3TC to ZVD + 3TC. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #257].

(3) Gallant JE, Hall C, Barnett S, Raines C. Ritonavir/Saquinavir (RTV/SQV) as Salvage Therapy after Failure of Initial Protease Inhibitor (PI) Regimen. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract 427].

(4) Ercoli L and others. HIV phenotype switching during antiretroviral therapy: emergence of saquinavir-resistant strains with less cytopathogenicity. AIDS. August 1997; volume 11, number 10, pages 1211-1217.

(5) Kempf D, Molla A, Sun E, Danner S, Boucher C, and Leonard J. The duration of viral suppression is predicted by viral load during protease inhibitor therapy. 4th Conference on Retroviruses and Opportunistic Infections, Washington, January 22-26, 1997 [abstract #603].

(6) Henry K and others. Levels of plasma HIV RNA measured by the Roche Ultrasensitive assay in HIV infected individuals with RNA levels below the bDNA detection limit. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #529].

(7) De Wolf F, Lukashov VV, Danner SA, Goudsmit J, and Lange JMA. Clearance of HIV-1 following treatment with three, four, and five anti-HIV drugs. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #384].

Retroviruses Conference Notes

By John S. James

The 5th Conference on Retroviruses and Opportunistic Infections, February 1-5 in Chicago, was one of the most important AIDS scientific conferences, yet it left unanswered most of the immediate questions of physicians and patients. Much of the progress has been in basic science, opening doors for future research and development but not affecting patient care immediately. On the whole, people came out of the conference at least as optimistic as when they went in; the HIV treatments which have greatly improved patient outcomes are still working as well as ever, and there are important new potential treatments and new research leads.

No one person could possibly cover all of the over 750 presentations--many given simultaneously with no tape or video recordings. Excellent in-depth reports are available, however (see "Retroviruses Conference: Where to Find More Information," in this issue). Here are some of the topics and presentations that caught our attention as particularly important. We plan more coverage in future issues.

* Clinical consequences of virological treatment failure. See interview with Steven Deeks, M.D., in this issue.

* New data on drug combinations now in use. There were no big surprises, but physicians and patients who are making medical decisions may want to review the latest information available. One of the best places to look is "Update from the 5th Conference on Retroviruses and Opportunistic Infections," a concise report by Steven Deeks, M.D., on the presentations of most interest to physicians. It is available on HIV InSite, the Web site of the University of California San Francisco AIDS Research Institute, Some of the major topics covered include d4T, double protease inhibitors, experimental twice-daily regimens of indinavir or nelfinavir, hydroxyurea, and two drugs now on expanded access and likely to be approved this year, efavirenz (DMP-266, Sustiva(TM)) and abacavir (1592). Also note the discussion of ACTG 320, and its possible implications for treatment of patients with advanced HIV disease. The review also includes brief presentations on two important potential drugs now in early human testing: bisPOC PMPA, and FTC.

* Hydroxyurea, especially when combined with ddI. It has become increasingly clear that this drug, which has long been used in cancer, will have a role in HIV treatment. However, there is little clinical-trial data on use by patients with CD4 count under 200. We are preparing a separate article on this drug.

* Zinc-finger inhibitors. The "zinc finger" is a structure found in HIV. Parts of it are identical across almost all retroviruses--meaning that it would be very difficult for HIV to develop resistance to a drug which destroyed this structure or prevented it from working. Many cells also have a zinc finger structure--but different from that of retroviruses--so any inhibitor would have to be selective. At least one zinc-finger inhibitor (CI 1012) is now in early human trials; no data on it was presented at the Retroviruses conference, however. About 150 articles mentioning zinc fingers havebeen published and are referenced in AIDSLINE; much of the early work on this class of drugs was done by the U.S. National Cancer Institute. This research has been low profile; it deserves more attention.

Fortunately one of the presentations at the Retroviruses conference(1) reached an audience of several hundred physicians and researchers. The speaker noted that there is an almost endless supply of potential candidate drugs--at least one which is non-toxic, can be taken orally, and reduces retroviral replication in animals. Another group from the National Cancer Institute also examined zinc finger inhibitors as a potential treatment;(2) two other posters looked at potential uses in vaccine development.(3,4)

* New technology for measuring how long immune cells live in the body. Until recently there has not been a practical way to directly measure how long CD4, CD8, and other immune-system cells live in people. A new method for tracking these cells in the body(5) is likely to be important for research on AIDS and other diseases as well.

The approach uses glucose with a non-radioactive isotope of either hydrogen or carbon, to label new cells as they are formed in the body. An isotope is an atom with a slightly different weight than ordinary atoms of the same element; chemically and biologically it behaves identically to ordinary atoms. Many isotopes are radioactive; this makes them easy to measure, but unsafe for human research. The non-radioactive isotopes now being used are safe; they can be measured with a machine called a mass spectrometer which is now commercially available for this purpose. This technique provides the best data yet on the dynamics of immune cells in the body, and may prove useful for clinical diagnosis as well as for research.

There were dozens of other conference presentations worth mentioning; we cannot list them all.


1. Henderson E and others. In vitro and in vivo activity of antiretroviral compounds attaching NC zinc fingers. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #007].

2. Huang M and others. Anti-HIV agents that selectively target the retroviral nucleocapsid protein zinc fingers without affecting cellular zinc finger proteins. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #643].

3. Rossio JL and others. Inactivation of HIV-1 infectivity with preservation of conformational and functional integrity of virion surface proteins. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #103].

4. Gorelick R and others. Full length SIV nucleocapsid mutant DNA vaccine: Immunization and challenge. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #535].

5. Cesar D and others. Direct measurement of CD4+ and CD8+ T cell proliferation rates in vivo in AIDS patients using a stable isotope-mass spectrometric technique. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, February 1-5, 1998 [abstract #273].

Retroviruses Conference: For More Information

By John S. James

In-depth information from the 5th Conference on Retroviruses and Opportunistic Infections is available through conference abstracts, online summaries, and lectures with slides.

Conference Abstracts

These are available through the official conference Web site, The search software works well. There is a small hassle in that you have to go through a registration process every time, with a password that you assign yourself and then need to remember. Also, the screens can be confusing, in that you may have to scroll around in order to find the buttons you need to get through the registration procedure. (The conference abstracts were also provided in advance to registrants in book form and on a disk, but these are not readily available after the conference. The abstracts are also not available on any other Web site.)

The searchable abstracts are particularly useful when you want to find out about a particular topic (such as a drug name) which lends itself to a keyword search. Be aware that all but a few "late breaker" abstracts were submitted months in advance; most of them are still correct today--even if not complete--because authors usually avoid factual statements which would be likely to change.

Online Summaries

Several different summaries of the conference, or certain parts of it, have been published on AIDS Web sites--sometimes in the form of courses with CME (continuing medical education) credit. These summaries are usually the fastest way to get both an overview and the details of those topics which received wide attention at the meeting.

All of the following are excellent. Here are some of their particular strengths:

HIV InSite,, reviewed the information most likely to be useful to physicians. When you get to the site, select the Retroviruses summary and analysis by Steven Deeks, M.D.--not the other Retroviruses link, which takes you to the official conference site.

Project Inform,, has detailed summaries of each day of the conference, written for the community, and will include slides prepared for its community forums. Project Inform's analysis has been more open than others in addressing problems with the scientific direction of the conference itself, reflecting broader problems in AIDS research--issues widely discussed but seldom made public.

Clinical Care Options for HIV,, has the most extensive report on the conference (enough material to fill about 10 issues of AIDS TREATMENT NEWS), organized into several CME courses. It includes background information to provide perspective on some of the conference presentations.

The Journal of the American Medical Association,, has both original reports and a file of Reuters news coverage about the conference. When you get to the site, select Newsline.

The Body,, has conference summaries from a number of authors, many with the Seattle Treatment Education Project (STEP).

The National AIDS Treatment Advocacy Project,, is preparing a summary which will include resistance and cross-resistance, adverse events, new protease inhibitors and other new drugs, and some of the pediatric presentations. We have not seen this report before going to press.

Lectures with Slides

About half of the talks given at the Retroviruses conference were recorded, and are available either by audiotape, or as Internet audio (but not as transcripts) through the official conference Web site, The other talks are not available unless you were in the room. Usually the ones you cannot get are the ones with new data; the most likely reason for the blackout is that if the lectures were released, some journals would later refuse to publish the researchers' papers, on the grounds that the data had already been "published" at the conference. For non-specialists, fortunately, the overview lectures and the symposia, which you can obtain, are usually the most valuable.

The lectures are best heard through the conference Web site, because the slides used by the speaker are displayed along with the audio. Also, the lectures are free through the Web site, while the tapes must be purchased. One is likely to find some software hassles concerning the audio transmission of the lectures (although not as bad as last year); it may take an hour or more the first time, to download special software which is required and to get the process going.

If instead you want to obtain the lectures on audio tape, they are available from Sound Images, Inc., in Englewood, Colorado; phone 303-649-1811, fax 303-790-4230. Ask for the audio tape order form for the 5th Conference on Retroviruses and Opportunistic Infections, Feb. 1-5, 1998. Although slides are not available with the tapes, most of these talks do not rely heavily on slides.

Opportunistic Infections: Major New Report

A 175-page in-depth report on opportunistic infections and their treatment today was released February 1 at the Retroviruses conference by the Treatment Action Group (TAG). THE OI REPORT: A CRITICAL REVIEW OF THE TREATMENT & PROPHYLAXIS OF HIV-RELATED OPPORTUNISTIC INFECTIONS, VERSION 2.0, by Michael Marco and many others, completely updates TAG's earlier report published a year ago.

Infections covered in the new report include herpes simplex, varicella zoster, cytomegalovirus (CMV) retinitis, CMV-associated neurological disorders, PML, tuberculosis, Mycobacterium avium complex (MAC), bacterial pneumonias, sinusitis, gastrointestinal bacterial infections, cryptococcal meningitis, Candida and other fungal infections, cryptosporidiosis, microsporidiosis, Pneumocystis carinii pneumonia (PCP), and toxoplasmosis; each section has extensive references, and discussion of major clinical trials when relevant. Other topics include the effect of protease inhibitor antiretroviral treatment on opportunistic infections, and research and policy recommendations.

"The most important message that could be delivered is the need for identification of persons at risk, so that PCP prophylaxis can be administered. The marked reduction in morbidity with this simple intervention is still one of the major advances in the care of HIV infected patients, and the continued high incidence of PCP in patients not previously known to be HIV infected tells us that we are not effectively reaching this group." Peter Frame, M.D., quoted on the inside cover page.

You can obtain a copy from the Treatment Action Group, 200 East 10th St. #601, New York, NY 10003, phone 212-260-0300, fax 212-260-8561. A $10 donation is requested to cover distribution costs.

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