Balance of Power

Greg Harris knew when he began to experience severe psychiatric side effects from his antiretroviral cocktail that he needed to change his medication regimen'and quickly. Harris, who has known he is HIV-positive since 1988, pinpointed the nonnucleoside reverse transcriptase inhibitor Sustiva as the root of his problems. Even through the drug appeared to be helping to reduce his viral load, he urged his doctor to replace it with a different antiretroviral agent. 'I became psychotic and suicidal. It was clear after a very short period of time that I could not handle it,' says the 49-year-old Chicago resident. Because Harris had exhausted most of his other treatment options by that point, his only choice other than a Sustiva-based cocktail was a multidrug salvage regimen that might be only partially effective in controlling his HIV infection. He chose the salvage cocktail. 'The Sustiva was just too much,' he says. 'I had to go off of it.' While Harris's case is extreme, it also highlights a growing trend in HIV medicine: fine-tuning highly active antiretroviral therapy, particularly to minimize the adverse side effects of medications or to simplify dosing requirements to make sticking to a regimen as easy as possible. And with 25 brand-name anti-HIV drugs available'some that combine two or more different antiretroviral agents in a single pill, such as Combivir, Epzicom, Trizivir, and Truvada'individualizing a regimen to fit each patient's specific needs is more possible than ever before, says Joseph McGowan, MD, medical director of North Shore University Hospital's Center for AIDS Research and Treatment in Manhasset, N.Y. 'Many patients will want a once-a-day regimen or have a preference for or against certain medications,' he says. 'Many also may be coinfected with hepatitis B or have anemia or have an opportunistic infection'all things that affect the drugs they need.' He also notes that an HIV patient's psychological and social factors play a role in determining which HAART drugs are best for them. Even an HIV-positive person's living arrangements are factored in. 'Therapy really is tailored around each person's specific issues,' he says. Fixing Failing Regimens The most obvious driving force behind a regimen change is that the combination does not fully suppress HIV'or it loses its ability to do so'particularly if it is the first regimen for a patient, according to Kathleen Squires, MD, the medical director of the Rand Schrader Clinic in Los Angeles. 'When that is happening, we talk to the patient to try to understand if they are not taking their medications, if they are having side effects, if there is anything they are not telling us,' she says. If the drugs are too hard to handle or are ineffective against the virus, a different combination is often used. Brian Risley, treatment educator at AIDS Project Los Angeles, recommends that doctors keep their patients on an antiretroviral regimen for 16 full weeks before deciding whether a particular combination is effective. 'I would also be testing consistently'every month or even every couple of weeks'to make sure there is a trend that the viral load is going down. As long as you see that trend, I would continue it' for four months, he notes. McGowan also would consider switching a first-line regimen if CD4-cell counts were not rising'at least minimally'even though viral suppression remained strong. 'That is a little more controversial,' he says, 'but it is something to consider when there are several other effective drugs still available.' Adjustments Down the Road But for HIV patients already on antiretroviral therapy'particularly those on second, third, or even later regimens'treatment adjustment decisions are more complicated, says Stephen Follansbee, MD, the director of HIV services for Kaiser Medical Center in San Francisco. Ideally, when a treatment-experienced HIV patient's regimen is changed, at least two'if not all three'of the new medications should be drugs to which the patient's virus has no resistance, Follansbee says. The difficulties begin to arise when patients, like Harris, are resistant to many'or all'of the available drugs. Brady Allen, MD, assistant clinical professor of medicine at Baylor University, says that if the patient has dangerously low CD4-cell levels or has developed an AIDS-related opportunistic infection, he often adds or swaps in a single new drug, such as Fuzeon, even if the patient is resistant to the others still in the regimen. 'Sometimes you just have to bite the bullet,' he says, 'and hopefully buy them some more time until other new drugs become available.' If possible, however, most HIV specialists will avoid making any regimen changes for their drug-resistant patients who have few or no remaining treatment options. Allen says sticking to a failing regimen that has some inhibitory effects can still slow immune system damage until new treatment options become available. Quelling Side Effects Oftentimes, an easier decision for clinicians and their HIV patients is to tweak an antiretroviral regimen to minimize or eliminate drug-related side effects'if they directly affect quality of life, could cause later complications, or are so severe that they threaten drug adherence. 'We may change the regimen, stop the regimen, or make a one-drug change,' Corklin Steinhart, MD, medical director of the Florida/Caribbean AIDS Education Training Center in Miami, says of the options usually available. A common one-drug change, for example, would be to replace the nucleoside analog Zerit because 'most people point the finger at Zerit' as one of the leading causes of facial lipoatrophy and other fat redistribution problems, Risley says. Another is to switch from a protease inhibitor to a nonnucleoside analog if blood-based cholesterol and triglycerides become dangerously high. Also, older protease inhibitors can often be swapped for a newer one, such as Reyataz, Risley says, because that drug does not boost blood lipid levels. Changes also can be made for some HIV patients if side effects such as nausea, diarrhea, fatigue, or peripheral neuropathy make it likely that doses will be missed or medications ignored altogether, McGowan says. 'Rather than risk missing doses, we'll try to swap off for something else,' he says, noting that about one of every 10 of his HIV patients will make a regimen change because of adverse side effects. That is precisely what happened with Rob Hadley, 42, of Chicago. He prodded his doctor to swap one protease inhibitor, Crixivan, for another when he began experiencing severe urinary side effects. 'The sludge, the Crix stones, made it difficult to pass urine,' he says. Hadley even went so far as to have surgery to put a stent in his penis to release urinary pressure before finally deciding he could no longer tolerate the medication. 'It was too intense,' he says. 'I was not going to put up with that.' Today, he says, he is on a successful cocktail of Norvir, Fortovase, and Sustiva'his fourth regimen. For Mia Stewart, her decision to avoid one particular drug was cemented before she even began antiretroviral therapy. 'Even though you can take Sustiva just once a day and I am really bad with remembering to take drugs, I was told you can have really bad dreams on it,' the 33-year-old St. Louis resident says. 'I am trying to finish school. I am working. I am doing things. I could not go for that.' Instead, Stewart and her doctor settled on a regimen containing Combivir and Viramune that is dosed in two pills taken twice daily. Simpler Versus Tried-and-True Surprisingly, though, not all HIV-positive people are as willing to make adjustments to their antiretroviral cocktails as Hadley and Stewart. Squires says that some of her HIV patients who are experiencing drug-related side effects choose to keep taking those drugs because of their effectiveness in holding viral loads low and CD4 counts high. Steinhart adds that while some of his HIV patients specifically approach him about simplifying to once-a-day drug schedules, others with fully suppressed virus are reluctant to switch to simpler regimens even when he believes such a change would not compromise treatment efficacy. 'Sometimes the regimens have become such an important part of their lives that we can do more damage than good by changing them, because they have done so well so far,' he says. 'We usually leave those folks alone as long as they know there are easier regimens they could take.' For these patients, adverse side effects can sometimes be lessened through lifestyle changes, such as improved nutrition and exercise, Allen says. The side effects also can be treated with other medications, such as lipid-lowering statin drugs for those experiencing elevated cholesterol and triglycerides, antinausea medications, antidepressants, and even painkillers for peripheral neuropathy. But Allen makes it clear to his patients that adding more drugs to their daily regimens may have negative consequences, including toxicities related to the new medications or increased medication costs and copays for the additional pills. 'You also have to be on the lookout for drug interactions,' he notes, 'because some of these drugs interact poorly with each other.' More pills are not always the best choice for patients who have struggled with adherence, Risley adds. 'According to research, one has to be 95% compliant or better with antiretrovirals to achieve full viral suppression and prevent drug resistance,' he explains. 'For some people, adding more pills to their regimen could affect their ability to stick to it.' Looking Beyond Meds While it is possible to prevent or eliminate certain drug-related side effects by fine-tuning a regimen, many HIV patients are instead turning to complementary and alternative therapies, such as herbal supplements, massage, acupuncture, and chiropractic services. For example, Action AIDS, Pennsylvania's largest AIDS service organization, spends about $220,000 a year to provide off-site massage as well as chiropractic and acupuncture services for about 250 ongoing clients, plus as-needed services for other agency clients, according to Kevin Burns, deputy executive director. Massage and acupuncture can help alleviate pain caused by peripheral neuropathy, he says. Acupuncture and chiropractic services also are helpful in addressing nausea, diarrhea, and other side effects of anti-HIV drugs. Moreover, complementary services can go a long way toward warding off stress and depression, which have been shown to increase illness susceptibility and speed disease progression, says Michael Curtis, executive director of the Heart Touch Project, a Santa Monica, Calif.'based group that provides free massage and compassionate-touch services to people with AIDS and other serious illnesses. 'We cannot just keep looking on HIV treatment success based on the fact that people are no longer dying of AIDS,' Curtis says. 'We have to help them improve their quality of life, help them feel less isolated, help them feel less depressed, and help support their overall physical and emotional health'not just their living.' Even what some would consider extraneous services can have a big impact on the overall well-being of HIV-positive people, says Shannon Wagner, the executive director of Being Alive in San Diego. In addition to complementary services like massage, chiropractic, acupuncture, and programs like Quantum-Touch and Magnetic Rollout'offered through Being Alive's Holistic AIDS Response Program'Wagner's organization also offers access to an on-site hair salon, a drop-in center, and tickets to recreational and entertainment events. 'These things might sound like fluff,' Wagner says, 'but they are the things that help keep people's spirits up, help them keep positive, help them feel good enough to keep their doctor's appointments, stick to their regimens'and maybe go into individualized counseling if that is what they need.' Body, Mind, and Spirit Jeffrey Leiphart, Ph.D., is another firm believer in the interconnectedness of mind, body, and spiritual health. He has developed a program, now in operation at Shanti in San Francisco and in five other California communities, that aims to boost immune-system function and physical health by addressing 17 psychosocial cofactors that he says affect the body's ability to fight HIV disease. Participants in the 16-week Learning Immune Function Enhancement program meet weekly for three hours to examine the cofactors through experiential exercises, role playing, and group discussions. Attendees formulate individual health action plans at each meeting to incorporate what they have learned into their lives. The anecdotal evidence from program participants is remarkable. 'People come up to us and tell us that their health is rebounding,' he says, adding that physicians also say patients who have gone through the program are doing better clinically than their other HIV patients. Also, formal program evaluation research by an independent firm showed that participants completing the program improved their psychological health, cofactor performance, immunity, and had reduced HIV symptoms.'A three-year clinical trial funded by the California State Office of AIDS is under way at four sites to gather scientific data on the LIFE program's effectiveness. Health officials in St. Louis and Kansas City, Mo., have already been convinced to start the program there, and plans are under way to launch it in South Florida and Massachusetts, Leiphart says. If the scientific data from the ongoing clinical trial is as encouraging as expected, he says, the program may be expanded to other states, even nationwide. Patient Empowerment Follansbee and other HIV specialists say services like those offered through Action AIDS, Being Alive, Heart Touch, and Shanti can play important roles in helping patients better cope with their HIV disease and'ideally'stick to their health and drug regimens. 'I encourage people to find nonpharmacological interventions, but I want to know what they are doing and what they are taking,' Follansbee says, 'because there can be some interactions.' Steinhart agrees but adds that it is up to each person to decide, through both traditional and complementary services, how best to fight his or her HIV disease. 'The approach I take as a physician is that it is my responsibility to make recommendations because I have the latest information and the experience,' he explains. 'But I feel very strongly that it is the patient who makes the final decision. The individual needs to feel that he or she has more control over what is happening.' Risley counsels all APLA clients to take a personal stake in their health and HIV treatment approaches'and urges every HIV-positive person to speak with their caregivers about any changes, additions, or subtractions they would like to make to their treatment, including to their anti-HIV drug regimens. 'You do not have to tolerate what is intolerable,' he says. 'There are a lot of options out there. Your lot is not to suffer.'