New drug combinations help patients whose HIV develops resistance after several different treatments

July 08, 2002

BARCELONA, Spain--Cocktails of anti-AIDS drugs have dramatically increased survival of individuals infected with HIV. But the virus often develops resistance to the drugs in people who previously have taken multiple combinations of the medications.

Now a multi-center, randomized, and placebo-controlled trial of 481 people infected with HIV, co-chaired by Dr. Scott Hammer of Columbia University and Dr. John Mellors of the University of Pittsburgh, shows that giving patients a new combination of drugs, which includes two protease inhibitors rather than one, can reduce the virus load in a substantial proportion of patients who already had taken several anti-HIV drugs.

"Control of virus load levels in the blood leads to an improved immune system and a greater period of health, delaying the opportunistic infections and death associated with HIV infection," says Dr. Hammer. Dr. Hammer is professor of medicine, Harold C. Neu Professor of Infectious Diseases, professor of epidemiology in the Mailman School of Public Health, and chief of the Division of Infectious Diseases at Columbia Presbyterian Medical Center of NewYork-Presbyterian Hospital. Dr. Mellors is professor of medicine, chief of the Division of Infectious Diseases, and director of the HIV/AIDS program at the University of Pittsburgh School of Medicine

The study results are being published online July 6 by the Journal of the American Medical Association to coincide with the International AIDS Conference in Barcelona, Spain. The study was supported by the National Institute of Allergy and Infectious Diseases-sponsored Adult AIDS Clinical Trials Group (ACTG).

In the ACTG 398 study, which took place at 31 participating medical centers in the United States, patients were split into four groups, each taking the protease inhibitor, amprenavir, and either a placebo or a second protease inhibitor (saquinavir, indinavir, or nelfinavir). A protease inhibitor interferes with an enzyme HIV uses to reproduce itself.

All participants also received drugs that act on the HIV reverse transcriptase enzyme: abacavir, a nucleoside reverse transcriptase inhibitor; efavirenz, a non-nucleoside reverse transcriptase inhibitor; and adefovir dipivoxil, a nucleotide reverse transcriptase inhibitor. Reverse transciptase is another essential enzyme the virus uses to reproduce itself in human cells. These drugs had not been taken before by the patients.

After 24 weeks, the investigators found that 31 percent of these antiretroviral-experienced patients with moderately advanced immunodeficiency could significantly lower their virus counts to below "detectable levels" with regimens containing four or five new drugs.

"The overall response rate in the study was modest but resistance in this experienced population is a difficult problem to overcome and we set a high standard of virus suppression (i.e., a viral load less than 200 HIV/RNA copies/milliliter) to show success," Dr. Hammer says.

On average, though, the patients showed more than a 90 percent reduction in their blood viral load--although they may not have achieved a 200 RNA copy/ml level. "The decrease should be associated with improved health," Dr Hammer says.

Certain subgroups of patients, however, did better than others: patients who took two protease inhibitors and those who had never taken a non-nucleoside drug before the study. Patients who had a higher-than-usual level of sensitivity to the non-nucleoside inhibitor, efavirenz, termed hypersusceptibility, had a better response than those with the usual level of sensitivity to the drug.

"The study results have clear implications for HIV-infected individuals who are planning their long-term treatment approach," Dr. Hammer says. "Reserving potent classes of drugs, if possible, rather than using all of them in a cocktail during first- and second-line treatments should improve the long-term response rates of patients to anti-HIV drugs."

The study also points to the continuing need for new types of drugs that have activity against HIV strains resistant to older drugs. "There are promising drugs on the horizon that should move the field closer to the goal of long-term viral suppression and clinical well being over many years, if not decades," Dr. Hammer says.

Columbia University Medical Center

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 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