HIV’s virulence seems to have gathered steam over time, according to a large study of the epidemic in Europe, aids map reports. This finding is in direct contrast to a small study conducted in sub-Saharan Africa that made headlines on World AIDS Day. Publishing their findings in The Lancet, researchers in the pan-European CASCADE study of 15,875 people with HIV examined key viral and immune system markers between 1979 and 2008 to analyze how the virus has adapted and changed throughout the population.
The researchers found that the average time individuals took to see their CD4 levels fall below 350 after contracting HIV has fallen from 7 years for those who seroconverted in 1980 to 3.4 years for those who did so in 2002. The estimated CD4 count following seroconversion was 770 in 1979 and 570 in 2002, indicating that HIV’s acute phase appears to have become more destructive to the immune system. The average viral load set point—the level at which the virus replicates following the acute phase spike—rose from 11,200 in 1980 to 31,000 in 2002. It appears there was a decline to 25,500 in 2008, however.
These findings suggest there is greater urgency to “test and treat” people for HIV, as the slogan goes, since people who contract the virus have a smaller amount of time before HIV disease progresses significantly. Treating the virus as early as possible would also yield significant benefits for prevention of the virus, since the higher viral set point means that untreated HIV is 44 percent more infectious on average.
While the African trial may be flawed because the study was so small and compared only two time points, it is also possible that both studies’ findings are valid. Because antiretroviral (ARV) treatment was introduced in sub-Saharan Africa more recently, African HIV may have evolved to favor less virulent strains that did not kill “hosts” before they could pass on the virus. In Europe, ARVs may have shaped the evolution of the virus such that strains that replicate more rapidly in the absence of treatment are more likely to get passed on, since once people go on treatment the chance of transmission plummets.
An HIV-positive resident of Berlin, Germany, Brown developed relapsed leukemia in 2006. To treat the leukemia, he underwent special bone marrow transplants that also rendered him genetically resistant to HIV. Brown’s HIV medications were stopped in 2007 and several years later he remains free of HIV.
Brown is historically unique but in recent years scientific journals and the popular press alike have published multiple claims of HIV cures.
In 2012, French scientists announced a “functional cure” of HIV when 14 patients who were treated within months of initial HIV infection remained clinically stable after treatment stopped. Similarly mild cases of HIV disease had been reported even in untreated patients, and unlike Brown the French patients still have detectable HIV in their bodies. Thus the French researchers likened a fairly common piece of good clinical fortune to a historically important cure, and added little more than confusion in the process.
Timothy Ray Brown, the ‘Berlin patient.’Kevin Lamarque/Reuters
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The same year Boston researchers announced that two HIV patients with cancer had undergone standard bone marrow transplants on HIV therapy, and afterward had unusually low levels of HIV in their blood. Preeminent scientists said it was “conceivable and maybe even likely” the Boston patients' HIV was gone, HIV medications were stopped, the virus rebounded, and several months after it started the Boston celebration came to an end.
In March 2013, doctors announced that an HIV-exposed baby from Mississippi who was treated within hours of exposure was considered cured as once-detectable HIV could no longer be found off of therapy. Scientists speculated HIV never gained a foothold in vulnerable immune cells. In July 2014 it was reported that the Mississippi baby relapsed, most likely because the virus had been lurking all along in those self-same cells.
Echoing the Boston experience, this year two Australian patients were called “HIV-free” and “cleared” of HIV after very low levels of the virus were detected in the blood after stem cell treatments. Both men remain on HIV therapy “as a precaution” so there is no definitive proof of anything more than highly effective therapy and an intense hunger to claim something approximating a cure.
None of these patients, with the exception of Brown, was cured of HIV. Yet in each case a cure has been claimed or the words used to describe the story were so similar to “cure” as to be indistinguishable to the untrained reader.
Why?
Desperation, for starters. HIV has killed over 39 million people so far and every year more than a million more are infected. There is no more urgent public health priority than the discovery of an HIV cure. As a result, when new and exciting HIV findings emerge scientists and journalists can abandon their usual caution and succumb to the temptation to use words like “cure” loosely.
We can’t afford to be complacent about HIV.Konstantin Grishin/Reuters
Even cool headed researchers are keenly aware that generating buzz can be the difference between generous funding or the closure of their labs. Salesmanship can devolve into exaggeration as the press conference begins. Journalists and editors, too, are tempted to generate more clicks and sell more papers by freeing the results they report from the scientists’ humdrum caveats.
Desperation and salesmanship aside, even the brightest and most cautious scientists and journalists can get fooled. Many honestly believed, for instance, that the Mississippi baby was free of HIV.
Whatever their motivations, premature intimations of a cure can be dangerous.
The credibility of the HIV research effort is undermined when retractions follow each exciting new announcement of a cure (or whichever phrase like “cleared" is that day’s facsimile). The confusion and skepticism created by repeated retractions can dampen research subjects’ enthusiasm to enroll in studies and even weaken research funding.
The intimations of a cure can also lead to complacency about HIV. Reducing HIV risk behaviors is always challenging, and it is harder when the potency of HIV treatments or the near-availability of an HIV cure make HIV infection seem like, as one newly-diagnosed man told me, “no big deal.” Modern treatments for HIV do keep millions alive for decades and we are closer to a cure than ever before but nonetheless HIV is most definitely a very big deal.
To preserve our scientific credibility, and support our prevention efforts, we should put the word “cure” on a shelf and let it gather a little dust. Someday, when we finally find a cure, a real-life, honest to goodness, checked and double-checked cure, then we can dust off the “C” word and let Timothy Ray Brown know at long last he can have some company in the world’s most elite club.
Until then, we should remember Margaret Heckler. As the Secretary of Health and Human Services, she helped announce Robert Gallo’s discovery of the HIV virus in 1984. Famously she concluded by predicting that we would develop an HIV vaccine within two years. Thirty years later our patients still don’t have an HIV vaccine, or a cure. The next time the lights go up and the microphones click on, let us remember that the way we celebrate progress today cannot forget the unfinished work we take up first thing tomorrow.
A new study shows that starting antiretroviral drugs within a year of detecting the virus decreases patients’ chances of developing AIDS. But many people who are infected don’t know it yet.
Nick/Flickr
“Two critically important issues in human immunodeficiency virus (HIV) therapeutics are when to start antiretroviral therapy and how well these medications restore immunity,” writes Dr. Timothy Schacker of the University of Minnesota in a recent issue of JAMA Internal Medicine. He is commenting on a study done by the National Institutes of Health, also published in that issue, that looked at when HIV patients started taking antiretroviral meds, and how that correlated with their immune health later.
The researchers studied the data of more than 1,000 patients enrolled in the U.S. Military HIV Natural History Study between 1986 and 2010. They noted how soon patients started taking antiretrovirals after seroconversion—the point after HIV infection at which antibodies to the virus can be detected in a person’s blood. To measure immune health, the researchers looked at patients’ levels of CD4 T-cells—a kind of white blood cell. When people taking antiretroviral medication see their CD4 counts increase to 500 cells per microliter of blood, that is “typically regarded as optimal immune recovery,” the study says.
But it’s not perfect. According to the study, in healthy, HIV-negative people, that count is more like 900 cells per microliter. So HIV-positive people whose CD4 counts are higher than 500 but lower than 900 cells per microliter could still have a less-than-ideal immune system and be at increased risk for developing AIDS, even if they’re taking the drugs. So for the purposes of this study, 900 cells per microliter was seen as the ideal target that doctors should shoot for when treating patients using antiretrovirals.
Starting antiretroviral treatment within a year or less of seroconversion was associated with better outcomes for the patients, especially if their CD4 levels were at least 500 cells per microliter when they started treatment. These people had a higher chance of getting to the 900 cells per microliter “normal” level and were subsequently at lower risk of developing AIDS. This wasn’t a guarantee—only about a third of patients who started the medication within a year of seroconversion reached normal CD4 levels.
Early intervention might also be easier said than done. According to the Centers for Disease Control and Prevention, one in five people with HIV in the U.S. don’t know they have it. When the infection is still new, they might not be symptomatic, or they may mistake their symptoms for something else. What’s more, only one in three adults, and one in four children, have access to antiretroviral medications.
“The importance of a public health strategy that includes frequent HIV testing in persons at risk and prompt initiation of [antiretrovirals] after diagnosis is underscored by [these] two findings,” the study reads.
In his commentary, Schacker notes that while this research shows a step that can be taken to increase some HIV patients’ health, it’s far from a perfect treatment protocol.
“Even if we were to accept a score of only one-third of persons as a success, it is unrealistic to think that we will routinely identify patients within 12 months of infection, especially in the parts of the world where this disease is most prevalent,” Schacker writes. “This sobering observation underscores the need to better understand the pathogenesis of HIV infection and use that information to inform drug discovery and rational policies for treatment.”
