No Benefit to HAART in Patients With a CD4 Cell Count Over 500

via medscape.com

Starting highly active antiretroviral therapy (HAART) in patients with HIV whose CD4 cell counts are above 500/μL does not slow the progress of the disease, according to results from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) study.

The study's findings were published by a writing committee for the CASCADE collaboration in the September 26 issue of the Archives of Internal Medicine.

The article lends weight to the argument that treating patients too early in the course of their infections can do more harm than good, Jay Levy, MD, a professor of medicine at the University of California, San Francisco, and codiscoverer of HIV, told Medscape Medical News. Many of the drugs used in HAART have strong adverse effects.

"Above 500, as far as I'm concerned, you have a long way to wait," he said. "I have been telling people, 'Be careful of treating too early.' You get resistance, and you get patients who are not going to stay on therapy."

At this time, the US Department of Health and Human Services guidelines say that antiretroviral therapy is indicated in all patients whose CD4 cell count is below 500/μL. The guidelines suggest considering the therapy for all patients from the time of HIV diagnosis.

For the observational cohort study, researchers from multiple institutions enrolled 9455 patients between the years 1996 and 2009, all of whom had not had HAART or developed AIDS at the time they were enrolled and had CD4 cell counts below 800/μL. The scientists enrolled new patients once every month, creating 161 sequential nested subcohorts.

The researchers then followed up the patients, noting the number of days until these patients either died or developed AIDS. If the patients initiated HAART, as nearly all did, the researchers noted the patients' CD4 counts at that point. The median follow-up time was 4.7 years (interquartile range, 2.0 - 9.1 years).

The authors found that patients who started HAART with CD4 cell counts from 0 to 49/μL were 68% less likely to die or develop AIDS. The advantage decreased to 52% in patients who started HARRT when their cell counts were from 50 to 199/μL, 41% in patients with cell counts from 200 to 349/μL, 25% in patients with cell counts from 350 to 499/μL, and −10% in patients with cell counts from 500 to 799/μL.

The research confirmed earlier findings on the benefits of the therapy in patients with cell counts below 500/μL, but conflicted with a 2009 study published in the New England Journal of Medicine by the North American AIDS Cohort Collaboration on Research and Design, which found benefits for patients with cell counts above 500/μL.

The CASCADE researchers acknowledged that their study is only observational, and a more definitive study would randomly assign patients with various cell counts to begin or defer HAART. Such trials are underway, but the results are not yet available.

Because the patients were not randomly assigned, there were differences between those who deferred HAART and those who started it. At baseline, those who started had higher viral loads, shorter duration of infection, and slightly lower CD4 cell counts compared with those who started HAART within each subcohort. However, they were also less likely to have a history of intravenous drug use and less likely to be coinfected with hepatitis.

In a commentary that accompanied the study, Harvard retrovirus researcher Daniel R. Kuritzkes, MD, lamented that the researchers were unable to study directly the effects of HAART on non-AIDS-defining HIV-1 complications such as cardiovascular disease, neurological disease, and other end-organ damage. "These complications may cause significant morbidity without contributing to mortality over the relatively short time frame considered herein," he writes. In addition, Dr. Kuritzkes explains, the CASCADE study did not measure the potential benefits of HAART on prevention of HIV-1 transmission.

However, he said the study provides important information that clinicians can use while awaiting the results of prospective randomized trials. "While awaiting more definitive data," Dr. Kuritzkes writes, "the pros and cons of starting HAART at CD4 cell counts above 500/μL should be weighed carefully by clinicians and patients."

Read the Abstract of the study here.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Treatment is Key to Prevention of HIV/AIDS, Doctors Say

Via UCSF, by Dan Fost.

Doctors fighting HIV/AIDS have a new strategy working for them: Use the treatment of the disease as a way to prevent it – a strategy borne of the growing effectiveness of that treatment in the three decades since the disease first emerged.

“Treatment revolutionized AIDS,” says Diane Havlir, MD, professor of Medicine at UCSF and chief of the AIDS program at San Francisco General Hospital and Trauma Center. “Treatment changed AIDS from a uniformly fatal disease to a chronic disease.”

And now, Havlir says, “today’s treatment is also prevention.” Timely treatment can stop the spread of HIV/AIDS in many ways. In patients, it stops the virus from progressing into AIDS, and it prevents damage to organs such as the heart, liver and kidneys, which occurs in untreated AIDS. Treatment also greatly reduces the risk of HIV transmission.

Havlir cites the most encouraging news to date, the National Institute of Allergy and Infectious Diseases’ HPTN 052 study, released in May 2011, which reported a 97 percent reduction in HIV transmission among discordant couples – couples in which one partner is HIV-infected and the other is HIV-negative – when the HIV-infected partner is treated with antiretroviral therapy relatively early in the course of HIV infection.

The so-called 052 study – conducted by the HIV Prevention Trials Network (HPTN) – released its results four years early because the prevention effectiveness of the antiretroviral drugs now commonly used to treat HIV infections was so clear-cut.

That news put one more arrow in the quiver of scientists and doctors looking not only to attack HIV, but to stop it.

“Certainly we’re hoping that the next 30 years of HIV can be the last 30 years, especially in San Francisco, where we have the community resources and knowledge to put an end to the epidemic,” says Grant Colfax, MD, director of the HIV Prevention and Research Section in the San Francisco Department of Public Health AIDS Office. Colfax, who trained at UCSF, is adjunct faculty at the university today.

Read the rest here.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Lifelong Antiretroviral Therapy Unsustainable, Experts Say; One-Time HIV Treatments Must Replace ART

via Medscape Medical News, by Robert Lowes

Although more HIV-infected individuals are receiving life-saving antiretroviral therapy (ART) 30 years after AIDS was identified, researchers must also find cures and vaccines to eliminate the need for this lifelong and challenging treatment, according to an article published online May 31 in the Annals of Internal Medicine by 2 leaders of the National Institute of Allergy and Infectious Diseases (NIAID).

Carl Dieffenbach, PhD, director of the NIAID Division of AIDS, and NIAID director Anthony Fauci, MD, write that lifelong, daily-dosage ART is not a sustainable strategy in a world where 2.5 million people become infected with HIV each year.

To help them stick to their drug regimen, patients receiving ART require a healthcare system capable of delivering long-term care similar to the model used in the United States to manage patients with diabetes.

In an obvious nod to developing nations ravaged by HIV, the authors write that the need for long-term care creates a formidable challenge for "resource-limited settings and for patients who lack adequate health care coverage." They note that ART is given to only 1 in 3 HIV-infected individuals in the world who need it.

Cure Possibilities

One solution, write Drs. Dieffenbach and Fauci, is devising a 1-time cure for HIV, which could fall into 2 different categories. Researchers could find a true "sterilizing" cure that completely eradicates the virus from the body or a "functional" cure that permanently suppresses the virus to a harmless level.

In the case of a sterilizing cure, researchers must solve the problem of cells remaining latently infected even though ART has reduced blood levels of HIV to near zero. When ART ends, these latently infected cells cause the infection to recur.

Investigators are experimenting with ways to flush out the virus from "this persistent reservoir" so it can be treated with ART. Key to the success of this strategy is the development of a simpler, more accurate way of measuring the latent HIV reservoir.

Despite its treatment limitations, ART nevertheless promises to play an important role in preventing HIV infection through preexposure prophylaxis (PrEP) and treatment-as-prevention, according to Drs. Dieffenbach and Fauci. They point to the CAPRISA 004 trial, in which a vaginal gel containing tenofovir lowered the risk for HIV infection in sexually active women by 39%.

Likewise, the iPrEx study showed that a daily regimen of emtricitabine, 200 mg, and tenofovir disoproxil fumarate, 300 mg (Truvada, Gilead Sciences), was 44% effective in preventing infection in men who have sex with men and in transgendered women. The risk for infection decreased by 73% in those who took their pills on 90% or more of the days in the study.

Cautious Optimism

An example of treatment-as-prevention, not discussed in the article, is a recent trial showing that ART given to a group of HIV-infected individuals — most of whom were heterosexual — with relatively healthy immune systems was 96% effective in preventing infection in their partners.

The "ideal cornerstone" of a prevention strategy, the authors write, would be a safe and effective vaccine. The quest for such a vaccine has met with repeated failures, although several recent advances have led to "a degree of cautious optimism." For example, researchers have found that sexual transmission of HIV often appears to begin with a single "founder virus" that differs from the various strains that develop over time in an infected person.

This insight may create new targets for vaccines. In addition, a 2009 vaccine trial in Thailand reported 31% efficacy in preventing HIV infection — a modest success that future trials can build on.

A vaccine that guards against all forms of sexual transmission — including blood-borne transmission — would work in tandem with a growing number of other evidence-based prevention strategies ranging from PrEP to adult male circumcision, according to Drs. Dieffenbach and Fauci.

"Researchers are unlikely to achieve transformative successes in HIV with a unidimensional approach," they write. "Instead, this will require various versions of combination prevention strategies, depending on the target population."


Source.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Antiretroviral Drugs Dramatically Reduce Risk of Passing HIV to Healthy Partners

via Health Behavior News Service, by Glenda Fauntleroy

When one partner in a couple is infected with HIV and the other is not, treatment with antiretroviral drugs can dramatically lower the chances of the infected partner passing along the disease to his or her mate, a new evidence review finds.

Patients with HIV receive a combination of drugs is given as part of antiretroviral therapy (ART) to stop progression of the disease. The new review discovered that when patients with HIV are on ART, their partners had more than a five-fold lower risk of getting the virus than in couples without treatment.

“We weren’t particularly surprised having followed this literature for awhile,” said reviewer George Rutherford of Global Health Sciences at the University of California, San Francisco. “The magnitude of the effect was somewhat surprising, though.”

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Welcome to Mapping Pathways

Mapping pathways is a new multi-national project that engages community, scientific, policy and government stakeholders and will establish a research-driven and global understanding of the emerging evidence base about antiretroviral ‘treatment as prevention’ strategies in the fight to end the HIV/AIDS epidemic.

A description of our work, including a list of the global partners, can be found to your right.

We want to engage you, and tap your ideas, thoughts, and opinions on this fascinating and complex topic. Stay tuned to this blog - and look for us on Facebook and Twitter - for more.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]