THE URGENCY OF PAIN CONTROL IN ADULTS WITH HIV/AIDS

Ten years ago, AIDS was a progressive fatal illness with a short prognosis. Today, antiretroviral therapy--where it is available-- has transformed HIV disease into a chronic illness, requiring effective and expert palliative care interventions to ease the symptoms of patients with HIV/AIDS in the developed and developing world.

In this issue, Peter Selwyn explains the importance of developing the knowledge and skills to deliver effective pain control and palliative care together with antiretroviral therapy to provide the best quality of life for patients with HIV/AIDS.

Giving priority to pain control and palliative care while managing HIV disease is an urgent need in an epidemic characterized by a high incidence of symptoms, lack of good pathophysiology data to explain many symptoms, a large population of patients with limited resources, and a significant percentage of patients with a history of substance abuse.

--Sophie M. Colleau, PhD


An interview with Peter Selwyn, MD, MPH*


* Peter A. Selwyn, is Director of the Palliative Care Program at Montefiore Medical Center as well as Professor and Chairman of the Department of Family Medicine at the Albert Einstein College of Medicine, Bronx, New York, USA.

Q: Can you briefly describe the trajectory of pain in HIV disease?
A: The human immunodeficiency virus (HIV) attacks the cells of the immune system and produces an unstoppable decline in immune function, if not treated. During the early stages of infection, when the CD4 count --a measure of disease progression-is >500cells/L, approximately 30% of ambulatory patients experience clinically significant pain. In people with advanced disease, when the CD4 count is <200cells/L, opportunistic infections and malignancies develop into a diagnosis of acquired immunodeficiency syndrome (AIDS) where pain is a common problem, affecting about 50 to 75% of people with AIDS and almost all patients in the last few weeks of life.

Q: Are the clinical characteristics of HIV-related pain comparable to those of cancer pain?
A: Pain in HIV disease has many similarities with cancer pain. Like cancer patients, HIV patients experience on average 2 to 3 types of pain at the same time. Pain is part of a constellation of treatable symptoms such as fatigue, weight loss, depression, anxiety, cough. Like cancer pain, HIV-related pain can also be due to disease: close to 50% of pain syndromes may be directly related to HIV infection or to the consequences of immunosuppression; for example, headaches come with cryptococcal meningitis; abdominal pain with disseminated mycobacterium avium complex infection. From 15 to 30% of pain syndromes are due to the side effects of the medications used to treat HIV (headaches related to zidovudine, or peripheral neuropathy related to dideoxynucleosides). The remaining 25-40% are unrelated to HIV or its treatment.

Q: What drives the pain treatment strategy for AIDS patients?
A: Sometimes treating the disease itself will eliminate the pain: for example anti-CMV therapy for cytomegalovirus esophagitis. More generally, the treatment should begin with a thorough assessment based on the patient's pain rating scale, and use the least invasive route. The goal is to achieve optimal patient comfort and functioning with minimal medication side effects. The three-step WHO analgesic ladder should guide the pharmacologic interventions. Adjuvant drugs can be used at each step of the analgesic ladder to enhance analgesia and treat concurrent symptoms that exacerbate the pain.

Q: AIDS patients frequently have a neuropathic component to their pain. Can you elaborate?
A: Peripheral neuropathic pain is clinically present in approximately 30% of persons with AIDS. It may be related to the HIV infection itself, especially in patients with CD4 counts <200 cells/L. It can also be related to toxicity from certain nucleoside analogues, such as didanosine or stavudine. Sometimes, it is due to the effects of a concurrent chronic illness such as diabetes mellitus, or immune-mediated inflammatory demyelination. The pain manifests as tingling and burning sensations. Patients complain of pins-and-needles sensation, shooting or lancinating pain, or a sensation that their feet are swollen and their shoes too tight.

Q: What are effective therapeutic options for painful HIV-related neuropathy?
A: Anticonvulsant drugs have been shown to be effective, specifically lamotrigine and gabapentin, but some patients do not respond or cannot tolerate these agents. Antiepileptic drugs used for neuropathic pain such as carbamazepine may be problematic because of adverse drug-drug interactions with antiretrovirals. A recent randomized controlled trial demonstrates that smoked cannabis effectively relieves chronic neuropathy associated with HIV [see abstract]. Opioids have not been systematically evaluated for painful HIV-related neuropathy, but studies show efficacy across a broad spectrum of neuropathic pain disorders.

Q: A number of studies have documented the undertreatment of pain in HIV disease. What causes this underestimation?
A: Actually pain in AIDS is both underdiagnosed and undertreated. The care of HIV patients tends to be driven by a focus on identifying and treating a specific infection and as a result the concern for pain often remains secondary. This puts many patients at risk for undertreatment. Studies documenting the undertreatment of pain in AIDS suggest that all classes of analgesics, particularly opioids, are underutilized in the treatment of pain in AIDS.

Q: Studies conducted in the US and Europe show that barriers to the treatment of pain can come from the HIV patients themselves. Can you explain?
A: Yes, some patients are reluctant to report pain or to take opioids. Others have expressed concerns about the side effects of opioid administration. We know that disadvantaged populations with HIV, including injection drug users and other substance users, the less educated, persons of ethnic minorities, the unemployed, and women tend to report more pain, and face more barriers to adequate pain management. Some patients may try to limit the number of "pills" they take or prefer to use nonpharmacologic interventions for pain relief.

Q: How are clinicians using this information to better manage pain in AIDS patients?
A: Patients can be reassured about the prevention and treatment of opioid-related side effects. Likewise, clinicians can work with patients to help identify effective and acceptable analgesic regimens. Since patients with HIV infection must often take several medications per day to fight the disease, many prefer using a pain intervention that requires a minimum of additional pills. Sustained-release preparations of oral opioids can provide 8 to 12 hours of analgesia and minimize the number of daily doses to control persistent pain; a transdermal opioid does not require taking pills at all.

Q: What other obstacles interfere with proper pain management?
A: Some patients cannot afford to have a prescription for analgesics filled, and others are reluctant to take opioids for pain relief because of concern that family, friends or physicians might assume they were misusing or abusing pain medications.

Q: Can you comment on the care of AIDS patients with a history of substance abuse?
A: Often physicians are reluctant to prescribe opioids to patients with substance abuse disorders. This is of special concern since many injection drug users may also have HIV/AIDS. There is definitely a risk that pain will be undertreated in this population. In fact, a recent study comparing AIDS patients to cancer patients found that patients with AIDS and pain and histories of substance abuse had higher global distress, higher rates of depression and anxiety, greater pain interference in daily functioning and lower pain relief from analgesics. Lower percentage of pain relief correlated with taking higher doses than prescribed, possible street drug use and using opioids to relieve other symptoms [see abstract].

Q: Treating pain in substance abusers clearly presents a special challenge.
A: Many clinicians are ambivalent or uncomfortable about prescribing opioids to substance abusers, a situation which often leads to underdosing. In reality pharmacologic tolerance suggests that opioid-dependent patients need higher doses of opioids, sometimes given at more frequent intervals than in non-opioid dependent individuals. Clearly palliative care clinicians need to work closely with HIV specialists and addictionologists to provide effective care to HIV-infected drug users.

Q: What is the impact of antiretroviral therapy (ART) on adults with HIV? Does ART improve symptoms including pain?
A: Antiretroviral drugs have had a very positive impact on the quality of life of patients and families; they have significantly extended good quality of life. In fact, the care of HIV patients with ART has been so successful in wealthy nations that clinicians have become less focused on pain and symptom management than they were 10 years ago when so many of their patients were dying.

Q: Are you saying that physicians are more interested in expanding access to ART and less interested in palliative care?
A: This decision should never have to be 'either..or', but in some respects this is how it has played out in developed countries with access to antiretrovirals. In some of these settings, some younger clinicians do not have the experience of seeing many patients die from AIDS, because most of their patients do so well on ART. However, as more HIV patients begin to falter while receiving antiretrovirals, physicians begin to recognize that not all patients respond to ART, and this opens the door to palliative care. In addition, because ART is prolonging survival, many AIDS patients are now vulnerable to die from liver cirrhosis and other organ failures, malignancies and other progressive, incurable diseases which did not use to be a risk in the past, because patients died before having the time to develop them.

Q: Does highly active antiretroviral therapy (HAART) contribute to pain?
A: Ironically yes. Because of HAART, patients survive longer and thus experience the pain syndromes common to HIV. Some of the same ART medications which help prolong life, such as didanosine and stavudine, can themselves cause peripheral neuropathies. Zidovudine can cause headache. This makes coordination between HIV care and palliative care challenging and complex.

Q: What about interactions between analgesics and antiretrovirals?
A: There are potentially dangerous interactions between anti-HIV drugs and medications prescribed for pain. For example the protease inhibitor ritonavir can increase levels of the opioids codeine, hydrocodone, oxycodone, methadone and fentanyl, and can result in drug toxicity. Again, the possibility of pharmacological interactions makes it essential to coordinate HIV-specific care and palliative care. This may also be true for anti-convulsants, benzodiazepines, and some anti-depressants.

Q: Is there any evidence that palliative care improves pain and symptom control for AIDS patients?
A: A systematic evidence-based review of 17 studies has demonstrated that home palliative care and inpatient hospice care significantly improve patient outcomes in the areas of pain and symptom control, anxiety and spiritual well-being [see abstract].

Q: What is the position of the WHO on pain care in HIV/AIDS?
A: The WHO recognizes palliative care as an "essential component of a comprehensive package of care for people living with HIV/AIDS as an important means of relieving symptoms that result in undue suffering and frequent visits to the hospital or clinic." More generally, WHO recommends a three-prong strategy for improving palliative care: 1. adopting a national palliative care policy + 2. training healthcare professionals and the public + 3. insuring that drugs for pain control and symptom management are available.

Q: Having analgesic medications available is clearly mandatory. If analgesics are in the medical facility, what could prevent clinicians from prescribing them besides their own lack of education about pain management?
A: Often, it is the absence of a rational drug policy or the absence of regulations allowing ready access of suffering patients to opioids. Strict regulations can mean that a supply of analgesics could remain locked in a safe, interrupting the supply chain. The example of Uganda [see abstract] suggests that government regulations can be changed (in this case to allow the importation of morphine powder), leading to the adoption of a national palliative care plan.

Q: You have been involved in publishing resources for education on palliative care in HIV/AIDS, right?
A: Yes. In the In the Clinical Guide on Supportive and Palliative Care for People with HIV/AIDS, we provide recommendations as far as systematic symptom management, creating good communication with patients and helping plan for the time when patients become very ill.

Q: Why is good communication a crucial element of palliative care?
A: Understanding the goals of the person infected with HIV, and of the family members affected by the illness is an essential first step in palliative care. The goal could be prolonging life, relief of symptoms, avoiding hospitalization, or putting affairs in order before death. Although the goal may change, the process of discussing values can only enhance the clinician-patient relationship.

Q: The guide has a chapter titled "Facilitating the transition to home-based and hospice care." Is that the planning you are referring to?
A: Yes. Patients and physicians are often uncomfortable discussing the possibility that treatment might fail and they put off planning for the end. In fact palliative care recommends having end-of-life planning discussions, and educating patients and families about hospice services. It is important that HIV clinicians develop the knowledge and skills to deliver effective pain control and palliative care together with ART to ensure the best quality of life for patients with HIV/AIDS.