Published in the Bulletin of Experimental Treatments for AIDS December 1996 issue, by the San Francisco AIDS Foundation.

December 1996 Table of Contents

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International AIDS Society-
USA Releases Treatment Guidelines for HIV/AIDS

by Harvey S. Bartnof, MD

An international group of prominent AIDS physicians has published a current set of treatment guidelines for HIV/AIDS in the Journal of the American Medical Association.

The guidelines recommend that HIV treatment be started for:

• Persons who have symptoms due to HIV. Such symptoms may include unexplained fevers, night sweats and weight loss. Other symptoms may be due to HIV-related conditions not defined as AIDS, including recurrent Candida infections of the mouth or vagina, or oral hairy leukoplakia.
  
  
• Persons with no HIV symptoms but a CD4 count less than 500 cells/mm³. The guidelines allow for deferring therapy if the CD4 count remains stable between 350 and 500 cells/mm³ and HIV blood plasma viral load remains below 5,000-10,000 copies/mL. However, many AIDS physicians would treat such people with the goal of achieving an undetectable viral load.
  
  
• Persons with a high HIV viral load, even if CD4 count is greater than 500 cells/mm³, and even if there are no HIV symptoms. Therapy is definitely recommended when viral load level is more than 30,000-50,000 copies/mL. Therapy should be considered when viral load is more than 5,000-10,000 copies/mL. Again, many physicians would treat in order to force the viral load to as low a level as possible -- ideally undetectable -- for as long as possible.
  
  
• Persons experiencing symptoms of acute HIV infection. The committee stated that, while still considered experimental, treatment with the most potent combination therapies seems warranted for those experiencing symptoms suggesting acute HIV infection (e.g., fever, sore throat, skin rash, muscle and joint aches). Enrollment in a clinical trial represents the first choice. At least 2 nucleoside analog reverse transcriptase inhibitors are recommended. The addition of a protease inhibitor or non-nucleoside reverse transcriptase inhibitor should be considered. Experimental successes that have led to undetectable viral loads did not always include a protease inhibitor. The current recommendation is to treat for at least 6 months.

To help prevent HIV transmission, treatment is recommended for:

• Pregnant HIV positive women. The committee endorsed current Public Health Service recommendations for using AZT. See article on perinatal HIV transmission, this issue.
  
  
• Health care workers who have an accidental occupational exposure to HIV. The committee endorsed the current Public Health Service recommendations. The recommendation is to treat with 2 or 3 drugs to which the viral strain has not been exposed. The triple therapy should include choices from 2 different drug classes.
  
  
• Following rape. The guidelines indicate that consideration of preventive therapy would be appropriate following forced sexual contact. While no studies have been done to show a benefit for treatment in such situations, this recommendation is quite similar to that for accidental occupational exposure in a healthcare worker.
  
  
• After accidental sexual exposure or accidental needle-sharing exposure. This issue was not addressed in the guidelines. However, at the satellite meeting where the new guidelines were described, members of the committee did address these concerns. Members indicated that similar recommendations should be made as are made for healthcare workers with an occupational exposure.

Issues to be considered in starting HIV treatment include the side effects of the drugs, long-term toxicity, the possibility of inducing drug-resistant virus, expense and the commitment involved in taking medications for an indeterminate length of time, probably years.

Which HIV drugs should be used?

For treatment of established HIV infection, the guidelines indicate that the era of AZT monotherapy is past. Studies have documented that combination therapy with 2 or 3 drugs is better than AZT alone. Potent combinations would include a protease inhibitor plus 2 reverse transcriptase inhibitors. Such triple combinations have demonstrated the largest reductions in HIV viral load levels. The current recommendation for triple therapy is for those patients at higher risk for HIV progression, including those with HIV symptoms, those with low or rapidly falling CD4 counts and those with high HIV viral loads. The only monotherapy for HIV treatment endorsed by the committee was ddI, although studies have since demonstrated greater reductions in viral load using combinations that include ddI.

Doctors have had the most experience with 2-drug combinations from the class of nucleoside analog reverse transcriptase inhibitors. Such combinations include AZT plus 3TC, AZT plus ddI, AZT plus ddC, and ddI plus d4T. Triple combination therapies with the most experience to date include indinavir/AZT/3TC, ritonavir/AZT/ddC, ritonavir/AZT/3TC, saquinavir/AZT/3TC and nevirapine/AZT/ddI. Many other double and triple combinations are being studied.

When should HIV treatment be changed?

There are 3 reasons to change HIV therapy:

1) The treatment is not working ("treatment failure"). Treatment failure occurs when one of the following occurs:

• HIV viral load has not decreased more than 3-fold compared to pretreatment levels or has returned to within 3-fold of pretreatment level. Viral load should be measured 3-4 weeks after starting or changing treatment and every 3-6 months thereafter (when the CD4 count is measured)
• CD4 count begins or continues to decrease in number or percentage
• Clinical progression of HIV disease occurs

2) Toxicity, intolerance or inability to adhere to dosing schedules occurs. Every drug has potential side effects or toxicities. Some of these overlap for different drugs. Many side effects or toxicities are minor or treatable. When the toxicities or side effects outweigh the benefits of a treatment, the treatment should be changed. Strict adherence to dosing schedules is important to avoid developing drug resistance, especially to protease inhibitors.

3) The current drug regimen is not optimal. For example, we now know that treatment with AZT alone is suboptimal and that combination therapy is better.

What should the treatment be changed to?

The treatment that should be used is the most potent combination that can be tolerated. What that combination is will depend in part on the reason for changing in the first place. Other considerations would include prior treatment history, currently available treatment options, stage of disease, underlying conditions, other concurrent medications, and cost and reimbursement issues. As a rule, for treatment failure, completely changing a regimen is better than merely adding one new drug to a failing regimen.

When should treatment be stopped?

Those with very advanced AIDS may have toxicity and quality of life issues such that aggressive HIV treatments no longer provide overall benefit. However, some very ill patients have improved clinically after starting a triple therapy including a protease inhibitor.

Carpenter CCJ and others. Antiretroviral therapy for HIV infection in 1996, recommendations of an international panel. Journal of the American Medical Association 276(2):146-154. July 10, 1996.

Harvey S. Bartnof has been a member of the Scientific Advisory Committee at the San Francisco AIDS Foundation since 1987.

Page last updated 17 December 1996