Top Eleven Tips for Dealing with Multi-Drug-Resistant HIV

By Gary R. Cohan, M.D., F.A.C.P.

Rates of HIV drug resistance have been rising sharply in recent years. This is not surprising given the number of different HIV medications that have been available for the past 15 years (20 are FDA-approved so far). According to a report in the New England Journal of Medicine, from 1995 to 2000, the percentage of patients who were resistant to at least one HIV medication quadrupled from 3.4 percent to over 12.4 percent. Another study by UC San Diego researcher Dr. Doug Richman showed that of patients who were taking HIV medications for at least two years, 78 percent had resistance to one drug and 51 percent had resistance to multiple drugs. Resistance testing has become so completely integrated into our standard of care for HIV that the Oct. 6, 2005 revised DHHS Guidelines for HIV Treatment stipulates that no patient or provider should consider making a drug switch from a failing regimen without first doing resistance testing.

The management of patients with highly drug-resistant HIV, although daunting, has become a field of intensive medical research. Our goals are to prevent further immune system deterioration and keep you from getting sick, to force the HIV virus into a weakened state, and to (eventually) establish maximal HIV suppression. The following are my "Top Eleven" tips for dealing with a highly drug-resistant HIV virus: ("the Do's and Don'ts"):

• DO NOT panic: This is not a death sentence. A 2005 British study showed that 97 percent of people were alive and kicking one year after finding multi-drug-resistant virus in their systems and 92 percent were still around after two years. Lots of research is going on and there are many new drugs in late-stage development to treat these drug-resistant viruses (see below for examples).
• DO NOT stop your current medications or take a "drug holiday": if you do this (probably with the thought that "this stuff isn't working anyway, so why should I bother"), the more destructive "wild-type" virus may emerge and will destroy your immune system very quickly. You must realize that "resistant" viruses are actually not 100 percent resistant to your medications. The medicines you are now taking - what we now call a "holding regimen" -- are forcing your virus to mutate into a type of HIV that reproduces at a much slower rate. In effect, even this "failing regimen" works for longer than you would expect because the mutated HIV is a weaker virus and has difficulty harming your T cells.
• DO get a drug-resistance test: resistance testing of your personal strain of HIV virus by a reputable laboratory can make a world of difference in picking the right new drugs. These tests must be done while you are still taking your medications (or within 4 weeks of stopping them). "Genotype" tests indicate which genetic mutations your virus has developed, while "phenotype" tests determine how well specific anti-HIV drugs actually suppress your virus. An excellent test that combines both of these technologies (and thus provides the most information about your personal virus) is called a "Phenosense-GT." This is the test that I order most often for my drug-resistant patients.
• DO consider the results from all previous resistance tests: since HIV resistance mutations are "archived" (like old books in the basement of a library) and never really go away, you should make sure that your doctor reviews all of your previous resistance tests to guide new drug selection. Even though certain mutations may seem to disappear on a new resistance test, they probably are still lurking around (in hard-to-detect quantities) and might sabotage a new drug regimen if not taken into consideration.
• DO keep 3TC (lamivudine, Epivir) in your "failing regimen" even if tests indicate you are "resistant" to it (with the M184V mutation) since 3TC has been proven to do two very important things -- it makes your HIV reproduce more slowly and it tends to make certain other HIV drugs work much better. Conversely, if you are failing NNRTI drugs like Viramune or Sustiva, you should stop them completely since these drugs do not help a failing regimen, may cause resistance to new drugs in this class and may just add cost and toxicity to the picture.
• Do NOT add a single new drug to a failing regimen -- adding the latest FDA- approved drug to a drug-resistant regimen is doomed to failure since three working (non-resistant) drugs are usually required to suppress your virus. Don't succumb to the temptation to waste an exciting new drug when no effective companion drugs are available.
• Do NOT start taking lots of over-hyped, unapproved "alternative" treatments or supplements: these usually do nothing good for your immune system, can interfere with the effectiveness of your current antivirals and, most ominously, they may cause liver, kidney, or other organ damage.
• DO have your doctor monitor your immune status closely: make sure that you don't go for more than 12 weeks without your doctor checking your T cells and viral load. People with HIV-resistant virus are sometimes under the impression that nothing can be done for them and stay away from medical monitoring for long periods of time. Unfortunately, doing so risks missing a major T cell drop and other preventable HIV-related complications.
• DO consider intensifying your current regimen with another protease inhibitor and/or boosting the levels of your current drugs with small doses of ritonavir.
• DO consider trying a whole new class or generation of drugs: there are many newer-generation versions of your standard medications (proteases, nucleoside RTI's and non-nucleoside RTI's) that may work against highly drug-resistant viruses (e.g. the new NNRTI's like capravirine and TMC-125, or the new PI's like tipranavir and TMC-114). Other exciting new classes of drugs block HIV's ability to attach to your T cells like the fusion inhibitors T-20, (Fuzeon) as well as the newer experimental CCR5-inhibitors and CXCR4-inhibitors. Make sure to team these new drugs up with other non-resistant drugs per your genotype results.
• DO consider waiting until three new, non-resistant antivirals are available. If your T cells are stable and your health is good, you should make no changes until you have a whole new drug regimen at your disposal (either via FDA-approved drugs or through a clinical research trial). In most cases of HIV drug resistance, patience truly is a virtue.

You can learn more about the latest in HIV treatment at the following Web site: aidsinfo.nih.gov/guidelines/adult/AA_100605.pdf.

Gary R. Cohan, M.D., F.A.C.P. is an HIV specialist. To contact Dr. Cohan, call (310) 657-6900, or via www.doctorcohan.com.

Fighting the Global War Against AIDS

By Michael Weinstein

As 2005 comes to a close, there is a great deal to be encouraged about in the global fight against AIDS. By year's end, one million people in the world will be treated for HIV. In 2001, when AIDS Healthcare Foundation began its treatment programs in Africa for a couple of hundred patients, it seemed like a faint hope that treatment would be available to the many, not just the few. In fact, when I think back to 1996 when the drug cocktail was discovered, activists were unsure that the U.S. government would cover everyone who needed the drugs.

While there is hope, globally we are still losing the war against AIDS. Three times as many people die of AIDS yearly as are being treated. Only five percent of the people who need treatment in the world are receiving it. Most people who are HIV-positive don't know it. Seven million people become infected every year.

If you look at what it would take to win this war, we come up lacking in every area. If we were truly approaching the war against AIDS as a war, things would look very different. Funding for global AIDS is chaotic -- each funding source has different rules and requirements. The U.S. government wastes hundreds of millions buying more expensive name brand drugs when excellent generics are available. Tens of millions of dollars intended to save lives in the developing world never leaves the Washington beltway, absorbed by contractors and government bureaucrats. Developing world governments are rife with corruption. Many technical issues like lab testing in rural settings, shortages of doctors and nurses and how to transport patients to clinics from distant sites are not being addressed.

Logically we should be taking the technology we have learned in coping with AIDS in the US and Europe and transferring that to the developing world. But instead of recognizing that community organizations have been the backbone of the AIDS response here and should lead the effort abroad, the U.S. is relying on academic institutions with no experience and little motivation. Non-governmental organizations cannot be so easily controlled and are therefore an inherent threat-whether it's at the Los Angeles County level or at the country level in a place like China.

The world is beginning to understand the importance of global health. The world is shrinking. As more and more 747s crisscross the world, everyone is at risk, whether from avian flu, HIV, West Nile virus or a microbe that hasn't been discovered yet. Global health is one of our biggest challenges and our greatest opportunities. And AIDS now takes its place as part of a worldwide public health movement.

AHF is now saving more than 10,000 lives at 21 clinics in the developing world from Mexico to India, plus providing technical assistance in a total of 13 countries across the globe. We are so grateful to have this opportunity. But, we would like to be doing so much more. As of yet we have not received any direct US government funding and little recognition from global institutions.

The good news is that a new vast constituency is developing at all levels. Celebrities, politicians, students, activists, business people the world over are getting involved and vast sums of money are beginning to be devoted to this awesome task.

If we regard the public health as if it were our own health, which it truly is, then we have a very good chance of winning these battles. Let us not look back years from now on global AIDS as we do about the holocaust, the genocide in Rwanda, or ethnic cleansing in Bosnia and wonder why the world stood by and did little to stop it.

We have the technical knowledge to stop AIDS the only question is whether we have the will.

For those of us involved in the global battle against AIDS, we do not look at it as a burden but as a magnificent adventure and we need your help. Consider how you can contribute. Is there any greater gift than having the opportunity to save a life?

Michael Weinstein is founder and president of AIDS Healthcare Foundation.

Not So Benign Neglect

By Phill Wilson

Last month my friend LeRoy Whitfield died from AIDS. He was smart, AIDS educated, and connected to the HIV treatment world. His death is yet another reminder that the AIDS epidemic is not over for black folks in America. Leroy's death is a commentary on how complex HIV/AIDS in "black face" really is.

In post-Hurricane Katrina America, everyone seems obsessed with whether George Bush cares about black people. Kanye West thinks he doesn't. Laura Bush thinks he does. After all, the first lady said, "I live with him. I know what he believes." Secretary of State Condoleezza Rice said, "Nobody, especially the president, would have left people unattended on the basis of race."

Maybe Laura and Condi are right. Maybe W. loves him some black folk. But who cares? It's the wrong question.

It is a deadly distraction for Americans to worry about whether the president or his administration likes us. What matters is, are they competent? Do they hire people based on their experience and expertise or based on whether they shared a dorm room with W. when they were in college? Are they capable, for example, of mounting an immediate and effective response to a natural disaster that happens to hit black folk especially hard? In this case, the answer is resoundingly no! While the jury may be out on the long-term governmental response to Hurricane Katrina, the verdict is certainly in on the government's immediate response.

On Thursday evening, Sept. 1 -- three days after Katrina hit New Orleans -- Anderson Cooper of CNN reported seeing the body of a black woman on the street being eaten by rats because she had been lying in the street for 48 hours and there were not enough facilities to pick her up. Race or class may not have anything to do with the Katrina relief efforts, but rats do not eat the bodies of white women in America.

So what do LeRoy and Katrina have to do with each other? Here are the facts. Dying people were left stranded in New Orleans after Hurricane Katrina -- and worse. With guns blazing, the police in Gretna, La., actually forced hungry, thirsty, and desperate people back into the flooding city. Most of these people were black.

In 2005, AIDS in America is a black disease. Nearly 1.3 million Americans are living with AIDS today, and about half of them are black. If that were not enough, 37 percent of the total AIDS deaths in the United States are black. Fifty-six percent of the new youth cases and nearly 70 percent of new HIV diagnoses among women are black. And most horrifying, a new five-city study found 46 percent of black gay and bisexual men were already infected with HIV, and two-thirds of them don't know they are infected and therefore are almost certainly not doing anything about it.

So what matters is not whether W. loves us or not. What matters is that he

didn't deliver on Katrina and he's not delivering on HIV/AIDS in America or any of the other social issues affecting our lives everyday.

Under George Bush's watch, the number of poor people in this country has surged by 4.5 million. As columnist Robert Scheer noted in the Los Angeles Times, there are now 37 million Americans, who are living in poverty. We saw some of them during the devastation of Katrina.

The poor are those in greatest need for access to health-care, but the administration has cut funding for federal HIV prevention programs, and recommended changes in the Ryan White CARE Act, the primary federal program that provides care and treatment for people with HIV/AIDS.

Bush also proposed a FY2006 budget that would irrevocably gut Medicaid, one of the few resources African Americans living with HIV have been able to turn to for treatment. This will almost certainly make the already awesome racial differential in survival rates among people with AIDS grow even larger.

We can spend all day speculating about whether or not Bush is racist. Mistake! If you go to a car mechanic who disconnects your brakes and you are killed in an accident, you are no more dead if he did it because he didn't "care" about you than if he was just plain incompetent. Natural disaster or public health disaster, mechanic or president, we need someone who will do the job right. Race may matter, but competency does also.

Phill Wilson is the founder and President of the Black AIDS Institute

(www.BlackAIDS.org).