AIDS TREATMENT NEWS Issue #361, February 28, 2001
John S. James

The March 1, 2001 issue of THE HOPKINS HIV REPORT has several short, focused summaries of some of the important treatment information from the recent Retroviruses conference (8th Conference on Retroviruses and Opportunistic Infections, Chicago, February 4-8, 2001). Written "for practitioners caring for patients with HIV/AIDS," it can also inform patients who have educated themselves about the disease. Because it targets busy people, the articles are short and to the point. This issue of THE HOPKINS HIV REPORT focuses heavily on antiretrovirals, and also includes an important section on hepatitis C.

Other major topics include the new treatment guidelines (see "Obtaining the New HIV Treatment Guidelines" in this issue), new antiretrovirals in development, when to start antiretroviral therapy, treating experienced patients, drug concentrations and interactions, adherence, and women's issues.

A table of contents with links to each of the articles is at: http://hopkins-aids.edu/publications/report/mar01_toc.html

For those without Web access, here are instructions for ordering by mail: "THE HOPKINS HIV REPORT is available for free upon request. All requests to be added to our mailing list should include complete mailing information and be sent to: THE HOPKINS HIV REPORT P.O. Box 5252, Baltimore, MD 21224, Attn: Distribution. Change of address should be mailed to the address listed above as well. All other correspondence should be sent to Mary Beth Hansen, Managing Editor, THE HOPKINS HIV REPORT, JHU Division of Infectious Diseases, 2700 Lighthouse Point East, Suite 220, Baltimore, MD 21224."

Some Highlights of the Johns Hopkins Retroviruses Conference Issue

"New Antiretroviral Agents" by Joel E. Gallant, M.D., M.P.H., summarizes many of the potential new antiretrovirals discussed at the conference -- including some still in laboratory testing, some in clinical trials, and a few in expanded access. You can get more information about any particular drug by searching for it by name in the abstracts of the Retroviruses conference (http://www.retroconference.org -- choose Conference Abstracts to get a search screen for the current year's conference; also, you can usually find an abstract by number through a search for the number) -- or in other databases, such as the National Library of Medicine, http://gateway.nlm.nih.gov, or AEGIS, (AIDS Education Global Information System), http://www.aegis.org

The drugs are categorized as follows (the examples here are not complete lists):

• NRTIs: Emtricitabine (FTC), DAPD, ACH-126,443
• NNRTIs: Capravirine, TMC-120, DPC 083
• Nucleotide Reverse Transcriptase Inhibitors: Tenofovir
• Protease Inhibitors: Tipranavir, BMS 232,632, Mozenavir (DMP-450), GW433908
• Entry Inhibitors: These include attachment inhibitors (for example, PRO-542), coreceptor (chemokine) antagonists (AMD- 3100, SC-351125 (SCH-C), SCH-D, and PRO-140), and fusion inhibitors (T-20, T-1249)
• Integrase Inhibitors: S-1360

"New Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents," by John G. Bartlett, M.D.

"For most clinicians caring for HIV-infected patients, the most useful aspect of the guidelines will be the tabular information on recommended regimens, food restrictions, side effects, side effect monitoring, recommendations for managing [drug] class adverse reactions, and dose recommendations for combination therapy."

The article also includes this note, which emphasizes the importance of seeing an HIV-experienced physician for one's care:

• "A preliminary study by the AETC National Resource Center [AIDS Education Training Centers, http://www.aids-ed.org/] indicates that about 98% of physicians with more than 20 HIV-infected patients are aware of these guidelines, and 96% have read at least part of them. However, among physicians with less than 20 HIV-infected patients, only 71% had heard of the guidelines, and only 52% had read at least part of them."
  
  
• Also see "When Should Highly Active Antiretroviral Therapy Be Initiated," by Timothy R. Sterling, M.D., in the March 1 Hopkins report. It discusses studies presented at the Retroviruses conference that contributed to the decision to recommend later treatment in the new guidelines -- including at least three separate studies which found an increased risk of death among those who waited too long and started treatment at a CD4 count under 200.
  
  
• "Antiretroviral Therapy: Naive Patients and Early Therapy," by Joel E. Gallant, M.D., M.P.H., includes many reports on individual drugs, developments in once-daily therapy, and when viral "blips" during therapy may be important.
  
  
• "Treatment of the Antiretroviral-Experienced Patient," by Gregory M. Lucas, M.D., looks at:
  
  
• salvage options for patients with failure of highly active antiretroviral therapy (HAART)
  
  
• switches from protease inhibitor (PI)-based regimens to PI-sparing regimens as a strategy to simplify therapy or minimize toxicity
  
  
• cross-resistance among nucleoside analogs
  
  
• "continuing HAART in the setting of persistent viremia."
  
  
• The section on drug interactions and pharmacokinetics ("Drug Transporter, Drug Concentrations, and Drug Interactions," by Adriana Andrade, M.D., M.P.H. and Charles Flexner, M.D., included:
  
  
• An overview of the complex but potentially important research on P-glycoprotein (P-gp), a molecular "pump" that can remove drugs from cells, preventing the drugs from working. Inhibitors of P-gp are being developed for cancer and other treatment. But P-gp appears to interfere with HIV as well as with drugs, meaning that inhibiting it could have both wanted and unwanted effects.
  
  
• A garlic supplement [taken twice a day for over two weeks in this study] was found to greatly lower the blood level of saquinavir (Fortovase®), to about half of what it had been without the garlic. The mechanism is not known, and it is not know what other drugs may be affected. For now, patients are being cautioned about using garlic supplements if they are taking protease inhibitors -- especially if they are using a regimen with saquinavir as the sole protease inhibitor.
  
  
• A study of indinavir (Crixivan) blood levels in patients using marijuana [4% THC cigarettes three times a day for 14 days] in the marijuana clinical trial at the University of California San Francisco found that indinavir levels may be decreased. But only one of the values was statistically significant, and no recommendations for changes in therapy were made.
  
  
• A test of how well laboratories in the U.S. and Europe measure blood levels of antiretroviral drugs found generally poor quality, [with only one of 13 labs tested being within 20% of the true value for all tests, and one result being off by 10 times; see Retroviruses abstract #734]. A quality-control program was recommended.
  
  
• "Women's Issues," by Jean R. Anderson, M.D., included new findings on reducing perinatal transmission, indications that HAART antiretroviral therapy may help improve outcome in cervical dysplasia, and discussion of the serious problem of increased incidence of some drug toxicities in women.
  

THE HOPKINS HIV REPORT also includes sections on hepatitis C co-infection (and hepatitis B), and on adherence. These are difficult to summarize. Hepatitis C received much attention at this conference. It is probably the most important co-infection today in persons with HIV [at least in the U.S.]. HIV accelerates progression of hepatitis C, and liver disease due to hepatitis C is becoming an increasingly important cause of illness and death in persons with HIV.

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