Oncologists are actively involved in several aspects of the care of patients with acquired immunodeficiency syndrome (AIDS), and so they should be aware of important quality-of-life issues such as pain management in this population. With the introduction of highly active antiretroviral therapies (ie, combination therapies including protease inhibitors), the face of the AIDS epidemic—particularly for those who can avail themselves of and tolerate these new therapies—is indeed changing. Even with advances in AIDS therapies, pain continues to be an important palliative care issue for patients with human immunodeficiency virus (HIV)-associated disease. For example, as the epidemiology of the AIDS epidemic changes in the United States, the challenge of managing pain in AIDS patients with a history of substance abuse is becoming an ever-growing challenge.
Studies have documented that pain in individuals with HIV infection or AIDS is highly prevalent, varied in syndromal presentation, associated with significant psychological and functional morbidity, and alarmingly undertreated.[1-12] Responses from a self-referred sample of AIDS outpatients indicate that these individuals experience many distressing physical and psychological symptoms along with a high level of distress.[13] Clearly, pain management needs to be integrated more fully into the total care of patients with HIV-related disease.
This two-part article, which will conclude in the July 2002 issue, addresses various aspects of pain management in AIDS patients, from assessment to treatment (both pharmacotherapeutic and nonpharmacologic), with special focus on the challenges of controlling pain in substance abusers with AIDS.
Prevalence of Pain in AIDS
Estimates of the prevalence of pain in HIV-infected individuals have ranged from 30% to more than 90%, with this frequency increasing as disease progresses,[4-8,12,14-16] particularly in the latest stages of illness. Studies suggest that approximately 30% of ambulatory HIV-infected patients in early stages of HIV disease (pre-AIDS, or category A/B disease) experience clinically significant pain, and as many as 56% have had episodic painful symptoms of less clear clinical significance.[5,7,12]
In a prospective cross-sectional survey of 438 ambulatory AIDS patients in New York City, 63% reported frequent or persistent pain of at least 2 weeks’ duration at the time of assessment.[5] The prevalence of pain in this large sample increased significantly as HIV disease progressed, with 45% of AIDS patients with category A3 disease reporting pain, compared with 55% of those with category B3 disease, and 67% of those with category C1-3 disease. Patients in this sample of ambulatory AIDS patients also were more likely to report pain if they had other concurrent HIV-related symptoms (eg, fatigue, wasting), had received treatment for an AIDS-related opportunistic infection, or had not been receiving antiretroviral medications (eg, zidovudine(Drug information on zidovudine) [AZT, Retrovir], didanosine(Drug information on didanosine) [ddI, Videx], zalcitabine(Drug information on zalcitabine) [ddC, Hivid], stavudine(Drug information on stavudine) [d4t, Zerit]).
In a study of pain in hospitalized patients with AIDS in a public hospital in New York City, over 50% required treatment for pain, which was the presenting complaint in 30% and the second most common presenting problem after fever.[8] In a French multicenter study, 62% of hospitalized patients with HIV disease had clinically significant pain.[7] Schofferman and Brody[16] reported that 53% of patients with far-advanced AIDS cared for in a hospice setting had pain, while Kimball and McCormick[15] reported that up to 93% of AIDS patients in their hospice experienced at least one 48-hour period of pain during the last 2 weeks of life.
Larue and colleagues[17] demonstrated that patients with AIDS being cared for by hospice at home had prevalence rates and intensity ratings for pain that were comparable to, and even exceeded, those of cancer patients. Breitbart and colleagues[4] reported that ambulatory AIDS patients in their New York City sample reported a mean pain intensity of 5.4 (on the 0-10 numerical rating scale of the Brief Pain Inventory) and a mean "pain at its worst" of 7.4. In addition, as with pain prevalence, the intensity of pain experienced by patients with HIV disease increases significantly as disease progresses. AIDS patients with pain, like their counterparts with cancer pain, describe an average of 2.5 to 3 concurrent pains at any given time.[4,6]
Frich and Borgbjerg[18] concluded that the incidence of disturbing pain in AIDS is high, specifically in the extremities, gastrointestinal (GI) tract, and head. In a study of 95 AIDS patients, the overall incidence of pain was 88%, and 69% of the patients suffered from pain that interfered with daily activity to a degree described as moderate to severe.[18]
Among AIDS patients approaching the end of life, 93% report experiencing pain and discomfort at some time during their final 2 weeks.[15] This percentage may be even higher, given that some pain and discomfort is likely to go unrecognized. Most patients in the study by Kimball and McCormick experienced at least one 48-hour period of pain and discomfort during the last 2 weeks of life; 88% received some sort of opioid analgesia, with the majority experiencing relief afterward.[15]
Overview of Pain Syndromes in HIV/AIDS
Pain syndromes encountered in AIDS patients are diverse in nature and etiology. As shown in Table 1, pain syndromes in HIV disease can be categorized into three types: (1) those directly related to HIV infection or consequences of immunosuppression, (2) those due to AIDS therapies, and (3) those unrelated to AIDS or AIDS therapies.[2,3,6]
In studies to date, approximately 45% of pain syndromes are directly related to HIV infection or consequences of immunosuppression; 15% to 30% are due to therapies for HIV- or AIDS-related conditions, as well as diagnostic procedures; and the remaining 25% to 40% are unrelated to HIV or its therapies.[6] The most common pain syndromes reported in studies of AIDS patients include painful sensory peripheral neuropathy, pain due to extensive Kaposi’s sarcoma, headache, oral and pharyngeal pain, abdominal pain, chest pain, arthralgias and myalgias, and painful dermatologic conditions.[5,6,8,10,12,14,16,17,19]
In a sample of 151 ambulatory AIDS patients who underwent a research assessment including a clinical interview, neurologic examination, and review of medical records,[6] the most common pain diagnoses included headaches (46% of patients, 17% of all pains), joint pains (arthritis, arthralgias, etc: 31% of patients; 12% of pains), painful polyneuropathy (distal symmetrical polyneuropathy: 28% of patients; 10% of pains), and muscle pains (myalgia, myositis: 27% of patients; 12% of pains). Other common pain diagnoses included skin pain (Kaposi’s sarcoma, infections: 25% of patients; 30% of homosexual males had pain from extensive Kaposi’s lesions), bone pain (20% of patients), abdominal pain (17%), chest pain (13%), and painful radiculopathy (12%).
Patients in this sample had a total of 405 pains (averaging 3 concurrent pains); 46% were diagnosed with neuropathic pain, 71% with somatic pain, 29% with visceral pain, and 46% with headache (classified separately because of controversy as to pathophysiology). When classified by pain type (as opposed to patients), 25% of episodes were neuropathic, 44% were nociceptive-somatic, 14% were nociceptive-visceral, and 17% were idiopathic pains.
Study patients with lower CD4-positive cell counts were significantly more likely to be diagnosed with polyneuropathy as well as headache. Hewitt and colleagues[6] demonstrated that while pains of a neuropathic nature (eg, polyneuropathies, radiculopathies) certainly comprise a large proportion of the pain syndromes encountered in AIDS patients (see Table 2), pains of a somatic and/or visceral nature are also extremely common clinical problems.
Pain in Women With AIDS
Our group at Memorial Sloan-Kettering has reported on the experience of pain in women with AIDS.[6,20] While preliminary in nature, our studies suggest that women with HIV disease experience pain more frequently than men with HIV disease and report somewhat higher levels of pain intensity. This may be, in part, a reflection of the fact that women with AIDS-related pain are twice as likely to be undertreated for their pain compared to men.[4] Women with HIV disease have unique pain syndromes of a gynecologic nature specifically related to opportunistic infections and cancers of the pelvis and genitourinary tract.[21] Moreover, women with AIDS were significantly more likely to be diagnosed with radiculopathy and headache in one survey.[6]
Pain in Children With AIDS
Children with HIV infection also experience pain.[22] HIV-related conditions in children that are observed to cause pain include meningitis and sinusitis (headaches), otitis media, shingles, cellulitis and abscesses, severe Candida dermatitis, dental caries, intestinal infections such as Mycobacterium avium-intracellulare and Cryptosporidium, hepatosplenomegaly, oral and esophageal candidiasis, and spasticity associated with encephalopathy that causes painful muscle spasms.
