Friday, April 5, 2013

"Breathprint": Your exhalation could help doctors diagnose you.

Most of us consider human breath only when it's clogging up our airspace. But there's more going on in there than a bunch of bacteria producing foul-smelling sulfur compounds. Your body jettisons all sorts of interesting molecules with every breath—compounds that can vary with the time of day or the ebb and flow of microbes in your gut  Now a new study shows that despite these variations, regular testing of breath can be used to establish an individual "breathprint" for each person, potentially unlocking a faster, less-invasive way to test for trouble within.

In a new open-access, peer-reviewed study out of ETH Zurich and the University Hospital Zurich in Switzerland, researchers had participants breathe into the business end of a modified mass spectrometer four times a day for 11 days. Participants had to refrain from eating, drinking, or brushing their teeth for half an hour before blowing. (No smokers allowed.) Interestingly, the scientists used data only from the last few seconds of each exhalation, as the first few seconds of any breath is mostly the "dead volume" in the upper respiratory tract. (Perhaps this isn't so surprising, as other biofluid tests—like urine pregnancy tests—recommend you pull a sample midstream.)

Each person yielded a stable "breathprint" over the span of eleven days. Which means beneath all our varying odors of garlic, coffee, and artificial spearmint, there lies a matrix of regular, detectable compounds that scream, This is my stink! There are many like it, but this one is mine!

Divining the secrets of the human body via breath isn't a new idea. The breath of diabetics sometimes smells noticeably fruity, thanks to the presence of acetone. In recent years, researchers have also had success identifying exhalation compounds linked to multiple sclerosisdrug use, and kidney disease. In Germany, another study revealed that dogs could sniff out lung cancer on a patient's breath with surprising accuracy.

While cancer-sniffing dogs sound amazing, they make bum lab partners. Or as the author of the study, Thorsten Walles, put it in a press release, "It is unfortunate that dogs cannot communicate the biochemistry of the scent of cancer!" The other diagnosis-by-breath studies, at least, can identify telltale molecules and then test specifically for them. The Swiss team is now looking to use similar methods in conjunction with their breathprint to create better tests for nasty diseases.

Recently, personalized medicine has become the topic of buzz, but genetics are just one piece of the human puzzle. The Swiss paper points to other factors affecting our health like lifestyle, interplay with gut microbiome, and circadian cycles. If researchers were able to better map a person's metabolome—the mess of 2,500 metabolites, 1,200 drugs, and 3,500 food components known to sometimes exist in the human body—it would give us another crucial piece of the puzzle.

For those fighting cancer or the chronically ill, breathprints could one day mean fewer blood-sample-pinpricks and inconvenient urine samples. Combined with genetic testing, those who are healthy but predisposed to certain diseases may be able to undergo regular breath testing to watch for warning signs.

It's enough to take your breath away.

Medical Emergencies at 40,000 Feet - Celine Gounder - The Atlantic

I was asleep, the plane dark as we flew over the Atlantic on our way from Johannesburg to São Paulo, when a familiar page came over the intercom: "Ladies and gentlemen, sorry to wake you. If there is a doctor on board, please hit your call button."

This wasn't the only time my sleep had been disturbed for a sick passenger. The first time was on a flight from Chennai to Frankfurt. I was still a medical resident and, as I slid out of my seat to help, I realized that I had no idea what medications, equipment, or assistance, if any, I would find. While relieved that it was nothing serious -- just a passenger who didn't feel well after mixing sedatives and alcohol -- I couldn't believe that no one else volunteered to help.

This time I was escorted to see a middle-aged obese Brazilian man. He was sweaty and dizzy, his shirt unbuttoned, his hands trembling. Another passenger helped translate. She told me that he was diabetic and had taken his medications that day. I checked his blood sugar with his glucometer and saw that it was normal. Then I checked his blood pressure -- no small challenge to do over the hum of the engines -- and was alarmed to find it very low. I nervously rechecked it, but it was again low, perhaps due to heart failure in the setting of a heart attack, or maybe a severe infection, or possibly internal bleeding. I went through the medical kit that the flight attendant had brought, gave him an aspirin and pulled out the IV kit. He needed fluids to support his blood pressure until we could land. Repeatedly I tried to place an IV in each arm and hand, growing more and more frustrated, but I simply couldn't locate a vein. At the hospital where I worked, I would have turned to a nurse for help -- any doctor will tell you that nurses are better at placing IVs -- but here I was alone. A flight attendant brought me hot towels to wrap around his arms to bring out his veins, but to no avail.

I sat with him, the oxygen cylinder that the flight attendant had also brought him between my legs, for the next several hours -- so much for getting any sleep. I coaxed him to drink water since I couldn't give him fluids intravenously while checking his blood pressure repeatedly. It was still low but stable. I was afraid that I might have to perform CPR on him if his blood pressure dropped further. How would we get him out of his seat and flat on the floor if it came to that? I asked the flight crew to have an ambulance waiting for us at the gate. As we prepared for landing, a flight attendant took back the oxygen tank. I protested, but she told me that it would be unsafe to leave it with us during the landing. Once on the ground, the flight crew allowed the other passengers to deplane first, even after I reminded them that their passenger might have a life threatening illness. By the time I helped the man off the aircraft, there were still no medical personnel at the gate to receive us. I was appalled.


Over the past seven years, I have responded to five in-flight medical events, three of which were true emergencies. It's estimated that a medical event of some sort occurs once for every 10,000 to 40,000 passengers on intercontinental flights. Information about these incidents is limited by underreporting, variable data quality, and the inability to determine what happens to patient-passengers when they leave the plane. In the United States, an airline is only required to report an incident to the Federal Aviation Administration (FAA) when a passenger dies or if the plane is diverted due to a death or medical emergency.

What we do know is that more Americans are flying than ever before: U. S. airlines alone transported 732 million passengers last year and by 2024 that number is expected to increase to 1 billion. At the same time an aging population means many passengers are taking to the skies with more medical problems. The result is an increase in in-flight medical incidents -- an upward trend that raises new questions about what ought to happen when a passenger falls ill while in transit.

Flying is stressful on the body. We carry heavy luggage over long distances between terminals, rushing to make our flights. We cross time zones, which may complicate our medication schedules. Some of us are afraid of flying or just see it as an opportunity to tune out the world and relax, and so drink alcohol or take sedatives.

While most medical emergencies occur due to pre-existing medical conditions or an acute illness, the aircraft itself can contribute to health problems. The cabin environment, which is pressurized to the equivalent of 6,000 to 8,000 feet above sea level, causes a 10 percent drop in blood oxygen saturation in the average traveler. Doctors generally advise healthy patients who are traveling to high-altitude destinations to allow at least a day at 8,000 feet to acclimatize before ascending further. Unfortunately many physicians aren't fully aware of the risks of flying, especially for their patients with chronic diseases. (If you can walk fifty yards at a normal pace or climb one flight of stairs without chest pain or significant shortness of breath, you are probably okay to fly without supplemental oxygen.)

Common in-flight medical events include dizziness, fainting, diarrhea, nausea and vomiting, shortness of breath, chest pain, palpitations, and headaches. Of course sometimes things get more serious. Heart attacks, other cardiovascular problems, seizures, and strokes are the most frequent in-flight medical emergencies requiring diversion of an aircraft. I have attended to two passengers with low blood pressure, a passenger who didn't feel well after taking Valium and drinking alcohol, a passenger who lost consciousness, and a flight attendant with chest pain and shortness of breath. On one occasion, we had to divert the plane for an unscheduled landing. On another, I was asked to come into the cockpit to speak with the ground medical team.

The FAA requires flight crews be trained to coordinate the response to medical emergencies, to use first aid kits, to be familiar with the contents of the emergency medical kit, to use an automated external defibrillator, and to perform CPR. But flight crews also rely heavily on the assistance of health care providers aboard the aircraft. Studies by the airlines and ground-based medical support services have found that a health care provider is available and responds in upwards of 80 percent of in-flight medical events. The truth is, though, that many health care providers find themselves attending to issues they don't see in their medical practices, and most have no specialist knowledge about aviation medicine or the medical resources aboard the plane. If asked, many health care providers will volunteer to help, especially if no one else is available, and this can lead to problems.

While returning from an international malaria conference, Dr. Michelle Hsiang, a pediatric infectious diseases specialist at the University of California San Francisco, attended to an elderly man suffering from diarrhea and dehydration on a twelve-hour flight from Sri Lanka to London. She was uncomfortable caring for an adult patient with several long-standing medical problems. "I'm a pediatrician, so I'm not used to taking care of adults," she said. "I think it's funny that they call for any physician since many are not board-certified to provide the kind of care that is needed."

Health care providers may also not be prepared to respond to an emergency because they board the plane as passengers rather than doctors. Like others they may take sedatives to help them sleep or consume alcoholic beverages. Dr. Larry Chang, an infectious diseases specialist at Johns Hopkins University in Baltimore, explained how this has impacted him: "I never take sedatives on flights because I feel like on almost every other international flight they ask if there's a doctor on board."


Sometimes the inconvenience to the physician-traveler can be more onerous. Dr. Hsiang said, "Usually when I've been on other flights, they let the person who is ill off the plane first. But [on one occasion] they left me with [a patient] until the very end. It was an international flight, so it took an hour for people to get off the plane. I had to wait with him as if I was his nurse." When she and the sick passenger finally got off the plane in London, there was no one there to meet them (an experience not unlike my own). Dr. Hsiang waited with the passenger for another hour. When medical help failed to arrive, she finally advised him to continue drinking fluids until he no longer felt light-headed when walking.

Health care providers responding to in-flight medical events and emergencies are protected under the 1998 U. S. Aviation Medical Assistance Act, which states that persons providing assistance in the case of an in-flight medical emergency are not liable for their actions unless they are guilty of gross negligence or willful misconduct. But many health care providers worry about their responsibility, if not their liability, and some may be reticent to help in an unfamiliar environment, outside of their area of expertise. They are also subject to the same inconveniences as other passengers if the aircraft needs to be diverted.

Volunteer health care providers also report widely variable assistance from the flight crew when responding to in-flight medical events. Dr. Lisa Rosenbaum, a cardiologist at the University of Pennsylvania, was asked to help when a pregnant woman started having regular contractions on a flight from Boston to Portland, Oregon. She advised an emergency landing, but like many volunteer health care providers, she was frustrated later by not knowing if the woman had delivered safely. "The flight crew was awesome," and she told me, "I got a card a couple months later from one of the flight attendants saying that the passenger had delivered safely after they landed, and that she and the baby were doing okay. I had no way of following up. It was so lovely that she took the time to write me a card."

In addition, when more than one health care provider responds to an in-flight event, there may be disagreement over how best to manage it. Dr. Julien Pham, a nephrologist at Massachusetts General Hospital in Boston, once found himself at odds with another volunteer who told the flight crew that the passenger seemed fine based on a cursory assessment. Meanwhile Dr. Pham remained concerned after having interviewed and examined the passenger, and he continued to check in on him periodically throughout the flight.

The FAA, which stipulates the medical supplies that airliners must have on board, last updated its regulations in 2001 to mandate that the majority of U. S. registered commercial aircraft carry automated external defibrillators (AEDs), which may be used to shock the heart back into a normal rhythm, and that some additional medications and equipment be added to the medical kits. The required medications include: a non-narcotic pain killer; IV fluids for dehydration or low blood pressure; an antihistamine to treat allergic reactions; an inhaler for asthma; aspirin and nitroglycerin for a heart attack; IV dextrose for low blood sugar; epinephrine for allergic reactions or asthma; and epinephrine, atropine, and lidocaine as an adjunct to CPR. The kits must also contain a stethoscope and a manual blood pressure cuff as well as some other supplies.

In the case of my Brazilian passenger, it would have been helpful to have a digital blood pressure cuff so that I wouldn't have had to struggle to listen for his blood pressure over the sound of the plane's engines. A digital blood pressure cuff would also allow a layperson to check blood pressure. Ideally, I would have had an oxygen saturation monitor when responding to the passengers with chest pain, low blood pressure or loss of consciousness; one might argue that you could give them supplemental oxygen, but when you're flying over an ocean and can't land for a few more hours, you want to get a better sense for the cause of a patient's symptoms. I have had to overhead page for a passenger willing to lend me their glucometer and test strips to check a patient's blood sugar, and I have found that the emergency medical kit may not include insulin. Passengers may become dehydrated from vomiting and diarrhea, but oral rehydration solutions, essentially highly concentrated versions of sports drinks, which are easier to administer in flight than intravenous fluids if the passenger can drink, are not usually available. Granted, space aboard aircrafts is at a premium, and it's unrealistic to expect that an aircraft be equipped like an emergency room. Based on my own experience, I'd drop the requirement for medications like lidocaine and atropine and items like arm and leg splints in favor of tools to obtain basic vital signs and to stabilize and treat common medical events.

While the FAA has no plans to review its requirements, a consortium of organizations including the International Civil Aviation Organization, the International Air Transport Association (IATA), and the Aerospace Medical Association are currently working with experts in emergency medicine to review their recommendations for what the kits contain. Regardless of whether changes are made to the kits, they will only be useful if the responding health care provider is made aware of their contents. In the case of my Brazilian passenger, I could have used an AED to monitor his heart rhythm, but I wasn't informed that there was an AED on board.


In addition to the goodwill of travelling physicians, all the major carriers in the U.S. have, for at least the past decade, also relied on ground-based physicians and nurses with experience in emergency care and additional training in aviation medicine. Based at centers including MedAire in Phoenix, the University of Pittsburgh Medical Center's STAT-MD program, the Mayo Clinic Aerospace Medicine program, and sometimes an airline's internal medical department, these experts work with the flight crew and volunteer health care providers on board over radio or satellite telephone to assess and stabilize sick passengers, to guide the decision whether to divert the airplane, and to organize the medical response on the ground. According to Dr. Paulo Alves, the vice president for aviation and maritime health at MedAire, these professional services are essential if we hope to provide passengers with a consistent level of care. "I don't think that it's professional to rely on health care providers to volunteer their assistance," he said. Handling a potential emergency, Alves says, takes more than just a physician's skills, it also requires "a good grasp of how to manage a medical situation in a resource-limited environment."

The trouble is, volunteer health care providers are often unaware they can turn to ground-based medical support services for help. I wasn't myself until recently. Having the support of ground-based medical services would have alleviated much of my anxiety about potentially having to "code" my Brazilian passenger in a difficult, unfamiliar environment, and they could also have helped coordinate a more appropriate response on the ground.

According to Dr. Claude Thibeault, medical advisor to the IATA, "If you are caught in a medical emergency on-board, the first thing you should do is to ask if the airline has access to ground medical support. If so, then ask the flight attendant to call them immediately." Unfortunately, studies have also shown that volunteer health care providers are much less likely to make use of these services than are the flight crew, and not necessarily for the better. I would suggest an even more proactive approach: the flight crew should call ground-based medical support services whenever they page for a health care provider on board the airplane. This would ensure that initial steps are taken to assess and stabilize the passenger in a more systematic way, that health care providers on board don't turn down the help for fear of appearing incompetent, and that accurate, detailed information on these events is collected consistently.

In addition, volunteer health care providers divert planes for medical events more frequently and unnecessarily (as measured by rates of hospitalization after landing) than other responders. Diversions are inconvenient for passengers, potentially dangerous depending on where the aircraft lands, and costly to airlines. An emergency landing of a domestic flight may cost an airline about $30,000, while that of an international flight, $70,000 to $230,000.

Only one of the medical events to which I have responded resulted in an unplanned landing. My husband and I were on a flight from Atlanta to Tucson over the holidays when a man sitting across the aisle from us slumped in his seat. The flight crew asked me whether we needed to land. I really didn't know how to respond and was more focused on trying to attend to the passenger. I was relieved that the crew went ahead and decided to land emergently in Houston.

Ultimately, how airlines respond to in-flight medical emergencies is an important measure of their customer service, and one of which we would do well to be aware.

Thursday, April 4, 2013

The Week I Had HIV - Slate Magazine

"You should go ahead and assume that you have HIV," the doctor said.
It was just before 7 on a frigid January evening. I was alone in my apartment in Washington, D.C.; I hadn't been expecting a call from the doctor. Several weeks earlier, I had come down with a fever and spent a good week laid up in bed. When I finally called my primary care physician, whom I'd chosen only a month earlier due to his proximity to my apartment, his receptionist signed me up for the next available appointment, which was a week away. Desperate, I went to a hospital, then an urgent care center, where a doctor suspected some kind of infection and prescribed a hefty dose of antibiotics. Within a few days, my fever had faded, but I decided to keep my appointment regardless. My new doctor, whom I'll call Dr. Smith, gave me a checkup, drew blood, and promised to run a full panel of tests. I hadn't realized that HIV would be one of them.
I realized it now. "Your ELISA test went up to positive," Dr. Smith told me, "so it triggered a Western Blot, and that came back indeterminate. Let me tell you what that means. You're probably early on in your infection, so it's not showing completely yet. But these results, in my experience, always indicate HIV positivity. Why don't you come in tomorrow morning and we can get an RNA test and a confirmation?"
"A confirmation," I asked, "that I have HIV?"
"Yes," the doctor said. "We should definitely assume right now that you have HIV."
This assumption would be proven false after a week—a week of anxiety, anger, and, most of all, confusion. My HIV test showed indications of early infection, signs portentous enough to prompt a doctor to diagnose me on the spot. Yet as I received more tests and more information, it became increasingly clear that Dr. Smith's verdict was a misdiagnosis—that I did not have HIV.
How can a test so common, so regulated, so accurate fail? How could I, a healthy adult with virtually no risk of infection, be misdiagnosed with HIV? And if it could happen to me, who else could it happen to?
Most HIV tests don't test for HIV. Rather, the primary diagnostic tool, an immunoassay, tests for antibodies that react to HIV. (Earlier generations of immunoassays were called ELISAs, pronounced "Eliza"; most immunoassays today are a newer generation called EIAs, but many doctors still call them ELISAs as shorthand.) The immune system floods the body with these antibodies soon after HIV infection as it attempts, in vain, to fight off the virus.
If an immunoassay test turns up HIV-related antibodies, it's considered "reactive." But a reactive immunoassay is not considered proof of an HIV infection. It must be followed up with a confirmatory test, usually a Western Blot. These tests also search for antibodies, but rather than turning "reactive" or "nonreactive," they detect about 10 different "viral bands." These bands are specific antibodies that bind to different components of the virus. If a Western Blot turns up two or more reactive bands, the patient is considered HIV-positive. If it turns up one band or several "equivocal" bands, the test is considered "indeterminate" and should be run again in about a month.
That monthlong wait speaks to perhaps the most insidious aspect of the AIDS virus: It hides. After infection, the virus conceals itself completely for about 10 days—the so-called "eclipse period." (A person in the eclipse period is almost certainly not infectious.) Once that phase ends, the virus begins attacking the immune system, provoking the antibodies detectable by immunoassays and Western Blot tests. Yet the process of producing antibodies takes time, and so there is an additional "window period" between antibody production and immunoassay reactivity. For today's fourth-generation tests, the time between infection and detectability is about 15 days; for third-generation tests, some of which are still used, it's 25; second- and first-generation tests need 50 to 60 days of infection to detect any antibodies. Western Blots require about two months of infection before turning positive.
This period of undetectability also happens to be the most highly infectious phase of the disease. Between 30 and 50 percent of all HIV transmissions occur during the window period. Thus, it presents perhaps the greatest challenge to combatting HIV: How can a highly infectious person be stopped from spreading the virus if he can't know he has it?
I received a third-generation immunoassay, which measured an antibody level of 1.23, just faintly reactive. (A level below 1.00 is considered nonreactive.) Following protocol, the lab then ran a Western Blot, which turned up "indeterminate." Dr. Smith told this to me when I went into the office the following morning. I asked for further explanation.
"Well," he said, looking at my lab report, "it's actually kind of a funny result. You have two nonviral bands but no viral ones. I've actually never seen a case like this."
"Could that mean I don't have HIV?" I asked.
"Probably not," he told me. "It probably means you're just seroconverting."
Seroconversion occurs during the window period of infection, when HIV attacks the immune system and it responds with antibodies. It is sometimes—though not always—accompanied by flu-like symptoms, such as high fever, respiratory distress, bodily aches, and night sweats. Seroconversion, in other words, is a hypochondriac's worst nightmare, masking a deadly virus with fairly routine symptoms. One distinction between seroconversion and a standard flu is swollen lymph nodes, a frequent symptom of acute HIV infection. But these can also be caused by a variety of other maladies.
"You said you were sick recently, right?" Dr. Smith continued. "Had a fever? That may well have been seroconversion. If so, you'll test a true positive soon."
I had, in fact, learned about seroconversion the previous week, when a different doctor had floated the idea—just possibly because I am gay. When my fever refused to budge after a week, my boyfriend took me to the hospital, where I was hooked up to a saline drip and given a battery of (inconclusive) tests. After I introduced the doctor to my boyfriend, a strange look came over her face and she excused herself. About an hour later, she came back, pulled the curtain closed, and sat down next to my bed.
"Before you go, one last possibility to consider is HIV," she said. "You do have a fever, which can be a symptom of acute HIV infection. It's called seroconversion."
Somewhat alarmed, I asked if any of my other symptoms matched up.
"No," she conceded. "Your lymph nodes are normal, and you don't have any respiratory issues. But still," she continued, lowering her voice and glancing toward my boyfriend, "it's something to consider."
Floating such a drastic diagnosis may sound like an overreaction, but in fact, the doctor was merely following generally accepted guidelines for HIV diagnosis. The CDC considers homosexuality high-risk in and of itself. Being monogamous and practicing safe sex doesn't matter much when you're a "man who has sex with men." What matters is your demographic. And my demographic makes me a likely vector for HIV.
Nine days after my visit to the hospital, my HIV test came back indeterminate.
Indeterminate Western Blot tests are a rare but intractable problem. Because they're used only as confirmatory tests, Western Blots have been the subject of much less technological advancement than immunoassays; it's more important to detect likely HIV than to confirm it beyond doubt. Some doctors and scientists see no place for Western Blots in the future of HIV testing; in fact, a few labs have begun to phase them out in favor for RNA tests. These search the blood for the virus itself, and have the immeasurable benefit of detecting HIV within only 15 days of infection. It is precisely because of this sensitivity and complexity, however, that RNA tests are rarely used as the first confirmation test: They remain prohibitively expensive for most labs and patients.
There are a number of reasons why a Western Blot could be indeterminate. Most indeterminate results arise from medical conditions that affect a patient's blood. Pregnancy, for instance, can cause a Western Blot to find traces of one viral band, called P-24. Autoimmune disorders can cause other viral bands to show up, as can the flu vaccine. Most of the time, these bands disappear in follow-up tests. If they don't but no further bands show up, the indeterminate result should be considered negative.
But there's another kind of indeterminate result, one so rare that Dr. Smith had never seen or even heard about it. This result indicates the detection of nonviral bands. These signal an error in the test itself. To run a Western Blot test, lab technicians grow HIV in a cell culture, isolate parts of the virus called antigens, and then expose them to a patient's blood serum. If the patient is HIV-positive, antibodies in his blood serum react to certain antigens, producing viral bands. But very rarely, the test can malfunction: Lab technicians may insufficiently purify HIV, allowing debris from the cell culture as well as antigens to be exposed to the blood serum. In turn, this debris—rather than the HIV antigens—may react with antibodies. The result: nonviral bands.
These bands do not indicate the presence of HIV. They don't even hint at it. In 1999, the National Confirmatory Testing Laboratory of the American Red Cross suggested that Western Blots with nonviral bands be considered immediate negatives, since "no individual exhibiting non-viral banding has been associated with either seroconversion detection of different HIV subtypes or other disease agents." The same year, the Association of Public Health laboratories stated that "non-viral bands should not be required to be reported [because] since 1991 no individual exhibiting non-viral banding has been associated with either early seroconversion, detection of different HIV-I subtypes, or other disease agents." And in 2000, the Blood Products Advisory Committee of the FDA proposed that nonviral band indeterminate Western Blots be considered completely HIV-negative, and thus safe to use in blood donations.
All of these groups recognized the same fact: Nonviral bands show up as a result of a lab error, not a blood infection. Yet none of their recommendations were ever taken. Many doctors are unaware of the nonviral bands and think them to be a sign of early seroconversion. Because the problem is so rare, it has attracted little research or attention from the press. When a patient receives this anomalous result, he is usually thrust into the formal process of an HIV diagnosis.
There are several ways to tell a patient he has HIV. Some doctors refuse to tell patients over the phone, choosing instead to make an appointment and tell them in person so they can quell the patient's panic and ask crucial follow-up questions. Others, however, believe that calling a patient and simply asking him to come in to discuss an HIV test is an obvious giveaway of an unwanted result, and that the news should simply be broken immediately, over the phone. This method has the benefit of ensuring that the patient knows his status whether or not he ever follows up. Rapid test immunoassays are quickly solving this conundrum: Clinicians can tell a patient his status in only 20 minutes. Rapid tests are popular in public health clinics but are not yet widely used by most primary care doctors, and so for now, the quandary remains.
Dr. Smith gave me his diagnosis over the phone and scheduled an appointment for the next morning. I spent that evening frozen in terror and confusion: There was simply no way, so far as I could see, that I could have been exposed to HIV. When I told my boyfriend, he was equally baffled: We each dug up the paperwork from our last two HIV tests, both of which were unambiguously negative. Nothing had occurred between those tests and this new one that could have exposed either of us to HIV. But this knowledge did little to allay the panic. We did not sleep that night.
The next morning at my appointment, Dr. Smith reiterated his strong suspicion that I was early into HIV infection and drew blood for a confirmatory RNA test. But he also suggested a rapid test immunoassay, which, by that point, should have turned positive. I sat for 20 minutes waiting for a second line to appear: Rapid tests contain colloidal gold, which reacts to HIV antibodies by producing a red line on a small screen.
As I waited for the test result, I began to think about what my life with HIV would look like. The virus, of course, is no longer a death sentence; those who have it can still live long, happy, mostly healthy lives. Moreover, the stigma once attached to HIV has largely dissipated, as HIV-positive people have rejected victim-blaming and empowered themselves both in their medical treatment and in the respect and decency they demand from society. The Internet provides myriad resources for those living with the infection, and virtual support groups foster a sense of community. No one has to face HIV alone, and no one should feel ashamed about being HIV-positive. If I did have HIV, I decided, I would not let it destroy my life. But I would much rather not have HIV.
After 20 interminable minutes, no second red line showed up on my test—a negative result. My confusion grew deeper, though my spirits started to lift. I had now received one positive, one indeterminate, and one negative HIV test. I still didn't like my odds. But the situation seemed slightly brighter than it had the night before. Six days later, I received mailed lab results from the urgent care clinic. Unbeknownst to me, they had run a highly sensitive immunoassay—and it was completely negative. My blood was not testing positive for HIV. The immediate sensation was not one of comfort, or even relief. It was bewilderment. Nothing that had happened to me seemed to make sense. And when it abruptly stopped happening, that made little sense, either.
Finally, more than two weeks later, my RNA test came back negative. Dr. Smith didn't explain the delay—the test takes less than a week—nor did he attempt to explain his original misdiagnosis.
"I have no idea why the Western Blot was indeterminate," he said. "But we should run one more immunoassay."
He ran one more immunoassay. It came back negative.
In all, I received six HIV tests in the span of less than a month. Without insurance, the process would have cost more than $2,000; an RNA test alone is about $500. Had the recommendations of the Confirmatory Testing Laboratory, the Association of Public Health laboratories, and the Blood Products Advisory Committee been adopted more than a decade ago, I could have avoided the entire experience. My indeterminate test was the result of a lab error; nonviral Western Blots always are. For the foreseeable future, patients who receive nonviral Western Blots will be misdiagnosed. And like me, they will live, however briefly, with the belief that they have HIV.
I asked Bernard Branson, the associate director for HIV laboratory diagnostics at the CDC, whether he thought indeterminate results would ever disappear completely.
"No test is perfect," he told me, "not even RNA tests." The CDC is currently working to develop immunoassays that dramatically cut the rate of false positives, false negatives, and indeterminate results, but there may always be a few cases like mine, no matter how advanced the technology. It's hard to know how many people get a false positive result. A 2005 study suggested a false positive rate from an immunoassay plus Western Blot of 1 in 250,000, but a lot of false positives are unreported, and the problem has not been the subject of much research.
"Why," he asked me in return, "are you interested?"
I explained to him my own experiences, my week of anxiety, and my hope that others in my situation might not face the same difficulties I did. As I spoke, I felt some of the confusion, the fear, the trepidation of that awful week lurch back into my mind. I had received my final confirmatory test more than a month earlier, but the pall of HIV still hung over my life in an ineffable way. Even now, several months later, I wake up some mornings with the same sudden panic I felt the moment I got the call.
"How can something like this still happen?" I asked Branson. That, at heart, was the question that had been haunting me. I wanted an answer beyond biology, beyond virology, an explanation larger than lab mistakes and hasty diagnoses. I wanted that week of my life back, and if I couldn't get it, I wanted to know why I lost it in the first place—why a widely used, highly sensitive test could malfunction, be misinterpreted, and bring me to the brink of despair.
Branson considered my question for a moment.
"How can it happen?" he said. "Bad luck."
When I finished the interview, I scoured my room for all of the results I had received and tucked away during my month of HIV tests. Then I tore them up and threw them away.