HIV Treatment Series
It's the Best Time to Get HIV, and the Worst
While the Virus Finds Its Way Around the Drugs, Newer Treatments Hold Hope
Except for the ones who won't. You see, as fast as scientists have devised new ways to thwart HIV's demonic tricks, some people with HIV have wasted these new weapons, allowed the virus to re-group, and then passed the newer, smarter HIV on to someone else. So is this the best or the worst time to get HIV?
No Worse Time to Become Infected With HIVLast February, the New York City Department of Health announced a disastrous new HIV infection. A man who had been infected as little as two months ago, and certainly no more than 20 months ago, already has AIDS, normally a late-stage condition that arises 10 years after HIV infection.
Dr. Thomas Frieden, the health commissioner, noted that the infected man is also already carrying a version of HIV with strong resistance to three of the four different classes of the medicines used to treat HIV.
Nearly all of the currently approved medicines fall into one of these three classes. When a patient's HIV develops resistance to any one drug, it typically has a head start on resisting other drugs from that class, too. Drug resistance normally brews slowly in an individual's body, as the internal tug of war between virus and medicines goes on over years. But it's also possible to become infected with a smarter HIV right from the start, from someone who had already exhausted some medicine's potential.
Even then a patient infected for just a couple of years normally wouldn't have to think about starting medicines yet. Current treatment guidelines advise letting a person's own body take up the fight as long as it can, and then sending in the cavalry of medicines when they're really needed.
Everyone is wondering whether the New York man's rapid progression to AIDS was due to weaknesses in his own immune system or due to a more virulent virus he caught in the first place.
Dr. Robert Gallo, credited with co-discovery of the AIDS virus, said that that the patient's quick progression might be "much ado about nothing," just an isolated instance of another rare person whose body succumbs to the virus rapidly.
It's also possible that the man's AIDS diagnosis will turn out to be premature. When a person first becomes infected with HIV, levels of the virus rise to enormous levels, and CD4 counts plummet. In some instances, patients develop opportunistic infections during this early phase of infection. Typically, their immune system will rebound naturally, bringing CD4 counts back up, though not all the way to pre-infection levels. If a patient's blood was screened during this "acute infection" period, it may show a CD4 count of less than 200 causing an AIDS diagnosis even though the patient's CD4s won't really settle down to that level again for many years.
So the New York man may or may not turn out to have CD4s steadily under 200. What about the multi-drug resistant virus? While it's true that this single case does not prove an epidemic spread of nastier virus, the New York man's drug resistance marks an ominous change. Normally, the few unlucky patients who progress to AIDS quickly do so because the virus outsmarts their immune system, sometimes even before they take any medications. These people usually still respond well to all classes of treatment. The New York man's resistant virus is only responding fully to one medicine (Fuzeon, from a different class), with an "attenuated response" to Sustiva. This is worrisome because it means he's not getting the benefit of a fully effective, three-drug HAART regimen. Partially successful combos with only one fully effective drug rarely work for long.
The unidentified man in his mid-40s used crystal methamphetamine, and is reported to have had unprotected sex with hundreds of other men. It's possible he may have been multiply infected, either in one night, or in successive nights.
HIV infection is not, as we once thought, like pregnancy. An egg can usually only be fertilized once, because it immediately sends out chemical signals telling other sperm not to enter after one has found its way in.
Similarly, people long assumed that when HIV finds its way into a white blood cell, the immune system's antibody response would prevent anyone else's HIV from entering the person at a later time.
But since the immune system takes from a few weeks to a couple of months to produce antibodies, a person who continued having unprotected sex in the weeks and months after initial infection could obviously catch additional strains of HIV, perhaps even accumulating a whole assortment of drug resistant variations.
For years a debate raged in the medical community over whether a person could be reinfected (also known as same clade superinfection) even after developing antibodies. Through the 1980s, physicians warned that this dangerous scenario was probably quite common. By 1994, they had reversed themselves to say that it probably happens only very rarely. In 2000, it seemed a case of reinfection and rapid disease progression had been discovered. By 2001, others questioned whether the blood sample was tainted.
This debate raged for so long because the technology to measure slight differences in a person's HIV only came about a few years ago. Last year debates gave way to reality when University of California researchers found some people living with HIV had become infected with someone else's HIV during the brief period that their blood was studied.
The patients, reinfected with the same clade (HIV 1-B) but different substrains, all suffered nearly a 100-fold increase in the amount of HIV in their bloodstream, and had a measurable drop in their immune system cells. The only patient who hadn't already developed treatment resistance in his own body acquired resistant HIV when he was reinfected.
Researchers warned that if this first group of 78 people studied is representative of patterns nationwide, then each year five percent of people living with HIV might be catching someone else's HIV on top of their own.
No Better Time to Get HIVIf you've recently been diagnosed with HIV, should you panic? Not necessarily. Just be sure to have your virus checked for resistance to any medicines twice a year (to see how well you will respond to specific medicines), and make certain that the version of HIV you caught from someone didn't already come with resistance built in. Built in drug resistance is discovered in about four-to-eight percent of newly infected persons, but in some regions up to 15 percent of newly infected people living with HIV have caught these craftier strains. Fortunately, in most instances, drug resistance will become an issue only when you're taking treatments, and even then usually only if you miss doses of your medicine.
In fact, today there's good news for people recently diagnosed with HIV. In the mid-1990s, researchers were insisting that just about every infected person undergo heavy treatment regimens from the day they were diagnosed. The belief was that by "hitting it early and hard," treatments could push HIV all the way out of the body.
The burden of side effects and complex dosing schedules, all while under the shock of one's new HIV status, was often overwhelming. Many patients missed doses of their medicines, triggering more dangerous strains of HIV to grow in their bodies. Scientists have now proven that patients who took eight out of ten pills on time back then were actually harming their bodies more than if they had just stayed off medicines altogether for a while.
The medicines back then were demanding (with frequent doses and lots of pills), but not very potent. The first protease inhibitor on the market only had four-to-eight percent bioavailability, meaning that even if you took every dose on time, you were still peeing out most of the medicine before it could fight HIV. That left barely enough medicine to keep your virus down. Newer treatments, especially so-called boosted protease inhibitors, wash over the virus like a tidal wave. With these medicines, patients have more wiggle room to be late with their doses, and maybe even miss an occasional dose.
While patients should try to take every dose on time, researchers have proven that resistance does not grow unless more than five percent of doses are missed, and that the benefits of the medicine aren't totally erased until a patient is late with or skipping 50 to 60 percent of doses.
For most people living with HIV, it's a new day. Take a look at some of the advances medicine has already made: in the first full year that protease inhibitors were prescribed, people living with HIV made 71,000 less trips to the hospital than had been the case just two years earlier. In total, people living with HIV spent nearly a million more days enjoying activities and friends instead of being cooped up in hospital beds!
From 1996 to 2001, as more and more people took advanced, three-drug combination regimens, AIDS death rates plummeted 80 percent. In the same five-year period, survival after an AIDS diagnosis had doubled in length.
The Most Critical Time to Manage HIV
Over a decade ago, researchers already knew that one-in-eight HIV-positive people would remain AIDS-free for 20 years. Only now has science ferreted out what is actually happening that makes some people advance quickly while others live well with HIV. Reinfection and multi-drug resistance are proving that acquiring HIV means you have to be more careful than ever to protect your body. A study in The Lancet last year found that people who acquire HIV more than once develop low CD4 counts (under 200), or progress to AIDS-defining illness or even death, all in an average of 3.1-3.4 years. On the other hand, those only infected once take an average of eight to 10 years to progress to AIDS.
New treatments will work for a long, long time, if you take medicines on time as prescribed. Up until recently, treatment combinations typically lasted just a year or two before collapsing under HIV's attack. But 98 percent of those patients lucky enough to start their treatment with the newer treatments (and to stay on the treatment) still have undetectable viral load six years later. In fact, a report at this year's 12th Retrovirus Conference finds that people diagnosed with AIDS anytime after 1998 live nine-to-ten years longer than those who were diagnosed during the mid-1980s. All told, today's HAART therapies "can lengthen the lifespan of persons with AIDS by nearly 15 years."
With wiser strategies about when to start medication, and better medicines available, newly infected people should be able to look towards a time line something like this: enjoy three to eight years without treatment, just checking your blood readings twice each year with a physician. Once it's time to begin medication, stick to your treatment regimen faithfully, and it will last for a decade. When the virus finally figures its way around that regimen, switch to a new regimen to buy another five to ten years. Your new regimen may well include novel therapies such as integrase inhibitors or antisense drugs. By the time the virus finds its way around these new therapies, the era of pill-based, daily medication may well be over.
Newer strategies are in the works that promise to change just about everything we know about treatment. Gene therapy (based on trim-alpha 5, perhaps, or a multi-targeted fusion and attachment inhibitor blocking CCR5 and CXCR4 co-receptors) may eventually allow a person to have all of his or her cells modified to become highly resistant to HIV's reproduction in the body. Scientists also think that they may one day be able to flush HIV out of its hiding places in the so-called sanctuary sites of the body. The virus will be forced to encounter ever-stronger medicines at full force in the bloodstream. When that day comes, everything we know about life with HIV will change.
Since cells have limited life spans, chances are this treatment would have to be repeated to cover new cells, but possibly not daily. CD4 cells have a half-life of two weeks, so a monthly infusion might one day be enough to keep the virus at bay. If HIV's reproduction is slowed enough, people may truly live a full life expectancy with no further complications.
So, if you became infected with HIV recently, the rules of the game are not to put yourself at risk for acquiring it again, and not to let it sneak around the medications. Careful living may well keep you healthy until HIV treatment advances to the level of permanently successful therapy.
Stephen Fallon is the President of Skills4, Inc., a healthcare and disease-prevention consulting firm that specializes in gay lifestyle and health issues by providing workshops, technical assistance, and grant writing services to community organizations and health departments. Visit his website at www.skills4.org. If you need sources for any medical information cited in his columns, e-mail him at firstname.lastname@example.org.
Editor's note: If you have been recently infected with HIV within the last six months, there are trials being developed to help research events occurring during acute and early infection, which may ultimately lead to a better understanding of the course of disease in an individual. The AACTG (Adult AIDS Clinical Trials Group) is developing three new trials with the Acute HIV Infection and Early Disease Research Program (AIEDRP). Go to www.aidsinfo.nih.gov for more information. -- JB
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