New finding may help doctors prevent HIV drug resistance

November 22, 2001

When an individual starts taking antiretroviral drugs for HIV infection, it is important to know as soon as possible if the drugs are adequately suppressing the virus. If they are not, some patients can develop drug-resistant strains of HIV in a matter of weeks, reducing the chance that a new drug regimen will be successful. Conventional wisdom, however, says doctors must wait four to eight weeks to accurately assess how well the drugs work.

But new findings suggest doctors can get the answer in one week, according to researchers at the National Institute of Allergy and Infectious Diseases (NIAID) and the National Cancer Institute (NCI). Their study shows the rate at which the virus disappears from the blood during the first week of therapy accurately predicts a drug regimen's long-term effectiveness in an individual. A report describing this work appears in the current issue of The Lancet.

"We now have a quick, simple and direct way of telling if the drugs are working," says Michael A. Polis, M.D., M.P.H., an NIAID infectious disease specialist and lead author on the Lancet paper. "In addition to heading off HIV drug resistance, this approach might also avoid exposing patients to the toxicities of antiretroviral drugs that aren't effective for them."

Currently, about 17 different antiretroviral drugs are available to fight HIV. They are prescribed in a variety of combinations because the fast-mutating virus quickly develops resistance to one drug alone. Many of the drugs work in a similar manner, however, so resistance to one drug can make the virus at least partly resistant to others. How well any drug will work in an individual is difficult to predict.

The standard approach to gauge a drug regimen's effectiveness in an individual is to measure the amount of virus in the blood after four to eight weeks of therapy. "Before our work, no one supposed an accurate prediction of drug efficacy could be made any earlier," says Dimiter S. Dimitrov, Ph.D., Sci.D, a computational biologist at NCI and senior author of the Lancet paper.

To monitor patients for drug resistance, doctors also analyze the virus's genetic material, RNA, to see if individuals harbor resistant viral strains. Trying to grow virus samples from patients in the presence of drugs is another way to check for resistance. "These tests, while useful, don't provide information as quickly or definitively as our measurement," says Dr. Polis.

Dr. Dimitrov and Polis's team mined the data of three previous clinical trials that tested a variety of antiretrovirals in HIV-infected adults and children. Once therapy began, the viral loads of those patients were measured daily. The researchers found that patients whose viral loads had dropped 50-fold or more at day six almost always responded well to the drug regimen long term. In contrast, patients whose viral loads dropped only five-fold or less at day six almost always responded poorly, that is, the virus concentration rebounded three months later. This single measurement accurately predicted therapy outcome more than 95 percent of the time.

"We are also trying to identify additional parameters that may help more accurately evaluate an individual's response to therapy," says Dr. Dimitrov.

These findings may be particularly important in light of recent reports that the years-long sharp decline in the number of Americans developing AIDS and dying from the disease appears to be leveling off, says Robert Yarchoan, M.D., study author and NCI researcher. "This news is evidence that the current crop of drugs are reaching the limits of their effectiveness," Dr. Yarchoan says. "One way to overcome that problem would be to develop new drugs, but another way would be to use the drugs we have more effectively. Our findings can help doctors to do that."

The scientists caution that a good result at day six is no guarantee a person will get better. "It is much easier to say when a therapy isn't working than to guarantee it will be ultimately successful," Dr. Dimitrov says. Dr. Polis adds, "Larger studies in more diverse groups of people need to be done to see if this approach will be useful in a real-life, clinical setting."
-end-
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Reference: MA Polis et al. Reduction in plasma HIV-1 RNA by one week following initiation of antiretroviral treatment correlates with longer-term efficacy. The Lancet 358(9295):1760-65 (2001).

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

Robert Kuska NCI Office of Communications (301) 496-6641

NIH/National Institute of Allergy and Infectious Diseases

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.