AIDS patients with serious complications benefit from early retroviral use, Stanford study shows

May 15, 2009

STANFORD, Calif. - HIV-positive patients who don't seek medical attention until they have a serious AIDS-related condition can reduce their risk of death or other complications by half if they get antiretroviral treatment early on, according to a new multicenter trial led by researchers at the Stanford University School of Medicine.

The study results could lead to widespread changes in treatment for HIV patients, particularly those diagnosed at an advanced stage, experts say.

"Even in San Francisco, one of the first epicenters of HIV in the United States, we still find that many people present late in the course of their illness with an opportunistic infection," said Mitch Katz, MD, San Francisco's director of health, who was not involved in the study. "This study shows that it is life-saving to treat those persons with antiretroviral drugs while they are still in the hospital. The results of this study will change practices throughout the world."

Some 60,000 to 70,000 newly HIV-infected individuals are identified every year in the United States, according to recently revised figures from the federal Centers for Disease Control and Prevention. A growing number of these patients, particularly minorities, youth, injection-drug users and those in poor rural areas, are being diagnosed late in the disease process when they've already developed life-threatening conditions, said Andrew Zolopa, MD, associate professor of infectious diseases and geographic medicine at Stanford and first author of the study. When these patients come for treatment of these complications, doctors are often reluctant to give them anti-AIDS drugs at the same time, fearing the two therapies could interfere with one another.

"A lot of people wait, thinking, 'Let's get the patient out of acute crisis, and then we'll deal with the underlying HIV infection later,'" said Zolopa. "But that answer is wrong. If we're more aggressive with HIV drugs, we can reduce AIDS-related complications and death by 50 percent. It's a substantial clinical benefit."

The study was conducted by the AIDS Clinical Trials Group, the world's largest clinical trial organization. Results will be published May 18 in the online journal PLoS-ONE.

William Powderly, MD, dean of medicine at the University College Dublin School of Medicine, said the study addresses one of the last, longstanding unknowns in the management of AIDS.

"Clinicians have long grappled with the question of whether or not early treatment with antiviral drugs will help people who come to the hospital with advanced infections, such as pneumonia," said Powderly, the study's senior author. "The answer is clearly yes. Early antiviral treatment for HIV improves the clinical outcome, including the likelihood of surviving in the next few months. It probably does so by improving the immune system and therefore adds to the ability to resist these infections."

The study findings, presented in abstract form at an earlier scientific meeting, are already starting to change clinical practices. The International AIDS Society, the CDC and the British AIDS Society all have adopted guidelines that recommend that early antiretroviral treatment be considered in patients with an opportunistic infection, Zolopa noted.

The study involved 262 patients at 39 sites across the United States, from Puerto Rico to Seattle. An additional 20 patients were enrolled in a hospital in Johannesburg, South Africa. Eighty-five percent of the patients were men whose median age was 28. They were an ethnically diverse group: 37 percent were black, 36 percent Hispanic, 23 percent white and 5 percent Asian.

The patients all had one or more opportunistic infection, with the most common ones being pneumocystis jirovecii pneumonia, cryptococcal meningitis and serious bacterial infections. Patients with tuberculosis were excluded from the study because it was unclear what the optimal antiviral treatment was for these patients, Zolopa said.

The patients, who were enrolled between May 2003 and August 2006, were separated into two groups: those who got antiretroviral treatment early and those for whom this treatment was delayed until their opportunistic infections had been dealt with. The patients were all offered antiretroviral drugs free of charge. The drugs for the study were supplied by Abbott Laboratories (lopinavir/ritonavir), Gilead Sciences (tenofovir and emtricitabine) and Bristol-Myers Squibb (stavudine).

The patients in the early intervention arm of the study were treated with ARVs within an average of 12 days, while those in the deferred group received the treatment within an average of 45 days after the start of treatment for the opportunistic infection. Among the patients treated early, there were 20 (14.2 percent) who died or developed another significant AIDS-related complication. That compared with 34 patients (24.1 percent) in the deferred group who died or suffered a new complication.

In addition, the patients in the early treatment group saw a much swifter recovery of their immune systems. The early group patients saw their T-cell counts, a measure of the immune cells destroyed by the AIDS virus, increase to more than 100 within four weeks. In the deferred treatment group, it took 12 weeks for the patients' T cells to reach that same level, the researchers reported.

"I was quite impressed at how rapidly these T cells could rise in these patients," Zolopa said. "By starting ARVs early you can effectively reduce the window of vulnerability where another AIDS-related complication could develop."

Zolopa said there was no difference between the two sets of patients in their adherence to their prescribed regimens. One concern in treating patients with ARVs soon after being diagnosed with AIDS is that they might not stick to their treatments and could then develop drug resistance. But adherence did not prove to be an issue, he noted.

"Starting the therapies early didn't scare people off," he said.

According to Zolopa, the study results probably provide some guidance for patients in developing countries, though each country would have to determine its own strategy for initiating ARVs in patients with advanced AIDS.

"These results do have important implications across the globe," he said.

Although the study did not include patients with tuberculosis, the most common AIDS-related complication among patients in sub-Saharan Africa, early ARV treatment has been shown in other, more recent studies to be of value in those patients with TB, Powderly said.

Zolopa said implementing the study findings could entail some logistical challenges, as hospitals will have to develop interdisciplinary teams, including pulmonary specialists, emergency physicians, pharmacists and others, in coordinating early treatment for these critically ill patients as they come into the system.
-end-
Other researchers in the study are Janet Andersen, ScD, and Lauren Komarow, both with Harvard School of Public Health; Ian Sanne, MD, of the South African College of Physicians; Alejandro Sanchez, MD, of the USC Keck School of Medicine; Evelyn Hogg with Social & Scientific Systems, Inc.; and Carol Suckow with the Frontier Science and Technology Research Foundation.

The study was funded by the National Institutes of Health through the Division of AIDS.

The Stanford University School of Medicine consistently ranks among the nation's top 10 medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

Stanford 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
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.