Win-win? Early ART could benefit individual patients, reduce HIV rates
Win-win? Early ART could benefit individual patients, reduce HIV rates
San Francisco takes a stand on issue
Evidence continues to mount in favor of starting HIV-infected patients on antiretroviral therapy (ART) soon after diagnosis. And San Francisco public health doctors are leading the way to making early treatment standard practice with new guidelines that recommend the practice.
The San Francisco Department of Public Health in San Francisco, CA, has new guidelines recommending that clinicians who work at the city's public health clinics discuss treatment options with their patients and then start treatment early if the patients so desire, says Diane Havlir, MD, chief of the HIV/AIDS division and Positive Health Program at San Francisco General Hospital and professor of medicine at the University of California, San Francisco (UCSF). Havlir also is the principal investigator of the AIDS Clinical Trials Group (ACTG) and director of the HIV Translational Research Training Program.
"Practice around the state and the country varies in terms of enthusiasm for early treatment," Havlir says. "However, it is clear that both providers and patients are re-evaluating the pros and cons of early therapy."
HIV clinicians and public health officials should focus less on the early treatment debate and more on the challenge of identifying HIV patients earlier in the course of their disease and engaging them and retaining them in care, Havlir says.
Damage in first year of infection
One new study suggests that some neurocognitive damage is done already by the time a person passes the first anniversary of his or her date of becoming infected with the virus.1
HIV clinicians in the United States are seeing much less dementia now than they did 10 to 20 years ago when they treated AIDS patients with severe impairment, notes Serena Spudich, MD, an associate professor of neurology at the University of California - San Francisco (UCSF).
"Now we're seeing a milder form of neurocognitive impairment, and this is supported by a number of very large studies," Spudich says.
For example, the CHARTER multisite study enrolled more than 1,500 patients who were given detailed tests. Investigators found that more than half had HIV-associated sensory neuropathy.2
"And most of those patients were on treatment," Spudich adds.
Other studies have had similarly alarming findings.
What these suggest is that patients either entered treatment with some neurocognitive damage or that their antiretroviral treatment did not stop progressive brain injury, Spudich says.
Spudich and co-investigators decided to test the theory that damage was done prior to initiation of antiretroviral therapy.
An analysis of 37 patients who had become infected within the previous year, but who had not been put on ART at the time of the study showed some interesting results: a majority of the subjects had impairment on at least one neurological test.1
"We did four simple neurological tests that have been validated as good screening tests for HIV-associated cognitive impairment," Spudich says.
"We simply looked at these patients at the time of the study, seeing some of them six weeks after infection and some a year after infection," she explains. "Then we administered these four tests to see if they performed normally at this early stage of HIV infection."
Most subjects were ART naïve at baseline, and they were all tested at baseline, six weeks, and each six months after that. Their tests included blood and CSF biomarker analysis, as well as results on the NPZ-4 tests, including timed gait, grooved pegboard, finger tap (non-dominant) and digit symbol tests.1
They found that most of the subjects had impairment when compared with published and well-validated, normal controls on one or more of the tests, she adds.
"We scored their performance and compared it to accepted norms for their level of education and age," Spudich says.
"We can't take away from these findings that the results were entirely due to HIV infection," she says. "We were comparing this group to perfectly normal controls who had no other confounding issues."
For instance, investigators did not know if their cohort's performance was affected by emotional state. Depression, bipolar mental illness, and substance abuse are more common in HIV cohorts than in the general public.
"In terms of interpreting these data, all we can say is 55% have impairment on at least one test, but we don't know if this is associated with some other premorbid confounding factor," Spudich says.
The study participants had a high level of education with everyone having finished college, and they included many executives. Also their drug use was not heavy, she notes.
"The fact that they tested as abnormal is concerning," Spudich says.
Investigators did compare the results of the subjects at six weeks to the 12 month follow-up, and they saw no statistically significant change over time.1
However, the lack of change could be of concern because it's typical for patients who take a neurocognitive test repeatedly to get better due to the practice effect, Spudich says.
"If you do a test once, and they come back in six weeks, they'll do better because they have done it before, and then six months later they'll do even better," she says. "You would expect the mean performance to have improved, and, in fact, it didn't."
So this cohort did not get better over time as would have been expected.
"We specifically found when we looked for signs of inflammation in the nervous system -- through spinal taps on these patients -- that the more inflammation the patients had, the worse they did on the neurocognitive testing," Spudich says.
"This suggests that the impaired testing performance was related to the level of inflammation in the nervous system," she adds. "We know inflammation is caused by HIV infection in the nervous system, and it's a major feature of HIV infection."
So these results add to the evidence that HIV infection can cause significant damage to patients' health from early on.
"Data like these, as well as data showing that patients with HIV who are untreated have higher risks of cardiovascular diseases are pushing doctors to earlier treatment," Spudich says.
But does ART prevent damage?
Such a policy remains controversial because researchers haven't proven definitively that if you treat people early they're protected from this damage, she adds.
Havlir is among the HIV clinicians who are convinced of the benefits of early treatment.
"My support for early treatment reflects the new insights in HIV disease that have emerged over the last few years," Havlir says. "We now know that HIV replication, from the very onset of acute infection, produces detrimental effects on the liver, kidneys, cardiovascular system, and the brain, probably mediated through immune inflammation."
Early treatment makes sense from several standpoints with the first being the fact that ART can shut down HIV replication and immune inflammation, delaying or preventing complications, she adds.
Also, the new generation of ARTs provides options that are tolerable and compact and that are less damaging than ongoing HIV replication, Havlir says.
"Third, we have the diagnostic tools to identify HIV drug resistance early and adjust therapy accordingly," she says.
The San Francisco Department of Public Health will be watching data involving infection rates, community viral load, and engagement and retention in care as the new initiative regarding early treatment is rolled out.
"We are recommending early therapy for the benefit of the HIV-infected individual," Havlir notes. "A secondary benefit of early therapy could be a reduction in new HIV infection rates, and recent data from HIV discordant couples would support this prediction."
- Peterson J, Lee E, Hecht FM, et al. Neurocognitive performance during primary HIV-1 infection. Poster presented at the 17th Conference on Retroviruses and Opportunistic Infections (CROI), held Feb. 16-19, 2010, in San Francisco, CA. Poster: 424.
- Ellis RJ, Rosario D, Clifford DB, et al. Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study. Arch Neurol. 2010;67(5):552-558.
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