Pain in HIV/AIDS a Major Global Healthcare Problem

Pain in HIV/AIDS a Major Global Healthcare Problem

HIV disease is a public health catastrophe of unprecedented magnitude in modern times

"Despite increased funding, political commitment, and progress in expanding access to HIV treatment over the past two years, the AIDS epidemic continues to outpace the global response," according to UNAIDS in 2004. In 2004 more than five million people became infected with HIV, more than in any previous year, and nearly 40 million adults and children around the world now are HIV-positive.

Already pandemic in sub-Saharan Africa, HIV/AIDS is Africa's worst social disaster since slavery. Sub-Saharan Africa contains 10 per cent of the world's population, generates one per cent of the world's income, and is home to nearly 70 per cent of the world's patients with HIV/AIDS.

Without the AIDS virus, life expectancy in sub-Saharan Africa would be 70 years: with it, it has declined below 30 years. The prevalence of HIV/AIDS is rapidly rising in Asia (e.g., India and China) and Eastern Europe (including Russia and other nations of the former Soviet Union).

Over 12 billion USD will be needed to effectively fight AIDS in developing countries alone by 2005, and 20 billion in 2007, but current annual spending falls well below half these values.

Challenges in controlling the most serious word has ever faced include behavior mutations in the virus that have thwarted to antiviral medications on an economic evolving infectious diseases such as infectious disease epidemic that the that promote its spread, ongoing vaccine development, limited access basis, and comorbidity with other tuberculosis and syphilis.

Pain is as multifactorial and widespread in patients with HIV/AIDS as it is in patients with cancer

Pain is second only to fever as the most common symptom in ambulatory persons with HIV/AIDS. Its mechanisms include nociceptive pain due to tissue injury as a result of inflammation (including autoimmume responses), infection (e.g., other viruses, bacteria, syphilis or tuberculosis) or neoplasia (lymphoma or sarcoma). Table 1 lists common sources of nociceptive pain in HIV/AIDS. Nearly half of pain in HIV/AIDS is neuropathic, reflecting injury to the central or peripheral nervous systems from direct viral infection, infection with secondary pathogens, or neurotoxie side effects of drug therapy.

Parallels between pain in HIV/AIDS and pain in cancer begin with the similar prevalence of pain in both conditions. Just as for cancer-related pain, HIV/AIDS pain treatment should whenever possible address the underlying disease itself. Like cancer pain, AIDS pain tends to be of more than one type, to involve more than one location, and to increase in intensity as disease progresses.

In a cohort of more than 500 ambulatory AIDS patients studied by investigators at Memorial Sloan-Kettering Cancer Center in New York, the prevalence of significant pain (defined as frequent, persistent pain for the prior two weeks) rose from 25-30 per cent in patients with early-stage HIV to about 50 per cent in ambulatory patients with a diagnosis of full blown AIDS.

Hospitalized AIDS patients have pain prevalence rates of 50-60 per cent, and those in hospice settings report a 60-70 per cent prevalence. Average and worst pain intensities have been reported as 5.7 and 7 respectively, on a 0-10 scale.

Other parallels between pain due to cancer, and pain due to HIV/AIDS, include an increasing prevalence of moderate to severe pain in persons with advancing disease of either cause, to a point where the majority of sufferers are eventually affected; a tendency towards stigmatisation of patients with pain arising from either cause, and worsening of suffering due to pain: phases in which acute, episodic, procedure-related or chronic stable patterns of pain may predominate; comorbidities such as viral or bacterial infections: and inadequate access to analgesic drugs such as opioids despite the fact that most pain in either condition can be managed using simple approaches based upon the WHO analgesic ladder. Although societal under recognition and under-treatment of pain applies both to patients with HIV/AIDS and those withcancer, those with HIV/AIDS are at greater risk. Other differences between patients with HIV/AIDS and cancer include their demographics (older persons are at greater risk for cancer, younger for HIV/AIDS), patterns of spread (sexual or drug-related transmission for HIV/AIDS), and higher likelihood of afflicting workers or parents of young children for HIV AIDS.

Highly active antiretroviral therapy (HAART) has changed the natural history of HIV/AIDS in wealthy developed countries but not resource-limited, developing ones.

Recognition of AIDS as a new, distinct clinical syndrome in 1981 evoked a worldwide response to identify its path ophysiological features, causative agent(s), comorbidities, and drug therapies to control if not cure the condition.

Patient-focused issues such as control of pain and other symptoms, and end of life care, became prominent early in the clinical, academic and research dimensions of- HIV/AIDS.

Much of the detailed knowledge of the prevalence, causes and therapies of pain in HIV/AIDS arose from work carried out in developed nations before the introduction of highly active antiretroviral therapy (HAART) in 1996. Since then, the natural history of pain in HIV/AIDS promptly diverged between developed and developing areas of the world.

In the former, prosperous countries, patients who adhere to HAART regimens for the most part have satisfactory if not normal CD4 counts, low viral burdens. and minimal symptoms so long as opportunistic infections or neoplasia are not present.

But for the majority of patients living worldwide with HIV/AIDS, HAART regimens are out of reach. In many developing areas, resources even to provide detailed descriptions of the epidemiology and mechanisms of pain in HIV/AIDS are lacking.

In light of the above, a comprehensive picture of the current global burden of pain in HIV/AIDS may best be produced by applying the detailed characterisations of pain types and origins gathered in developed countries in the pre-HAART era, to the total numbers of persons known to be affected globally with HIV at present.

A similar strategy might be employed, for example, to estimate the detailed global burden of cancer-related pain by using data on the occurrence of cancer pain according to type and stage of each tumor gathered in developed nations, and applying such estimates to the total number of individuals with a range of tumor diagnoses around the world.

Though not sensitive to variations in the natural histories of HIV/AIDS in different locales with regional variations in comorbid infections, health infrastructure and resources, nutritional status, per capita income and other factors including genetic variation in response to the disease or to analgesics, this approach is likely to yield conservative estimates for HIV/AIDS-related pain burden when applied to developing countries.

Many pain syndromes, affecting most organ systems, have been described in patients with HIV/AIDS

Most organ systems are potential targets for HIV. comorbid pathogens, or side effects of reatment. Thirty per cent of patients with HIV/AIDS have cardiomyopathy from lymphoid infiltration, and roughly the same number have left ventricular dysfunction. Pericardial disease (including tuberculous pericarditis) affects 10-30 per cent of those with HIV/AIDS.

Hyperlipidemia or diabetes mellitus are adverse effects of protease inhibitors. Half of new cases of HIV/AIDS present with a pulmonary process: these include pneumocystitis carinii, tuberculosis, other bacterial pneumonias, or interstitial pneumonitis.

Kaposi's sarcoma or non Hodgkins lymphoma may manifest in the lung. Gastrointestinal pathology and symptoms of HIV/AIDS are legion, ranging from oropharyngeal Candida albicans or cytomegalovirus, to diarrhea from enteric pathogens or opportunistic organisms, to liver disease from drug treatment.

Kaposi's sarcoma, or other viruses (Hepatitis B and C) or mycobacteria. Glomerulopathy, nephrotoxicity from medication, and acid base and electrolyte disorders as well as adrenal insufficiency are all described in HIV/AIDS.

Finally, the spectrum of neurological symptoms reflects direct viral infection of brain or nervous tissue (HIV is trophic for both), concurrent infections such as syphilis, primary lymphoma of the central nervous system, or progressive multifocal leuokoencephalopathy.

Headache, along with any other symptom in HIV/AIDS, must be evaluated in the clinical context as well as the CD4 count: values less than 200 per mm' raise the index of suspicion for more serious causes.

Pain in HIV/AIDS should be assessed to determine its origin(s) and mechanism(s)

For those persons with HIV/AIDS whose pain is not the result of a process with an obvious surgical or medical response such as drainage of an abscess or drugs for herpes zoster, every effort should be made to base therapy upon the origin and mechanism of the pain. Of the cohort of patients studied by the Sloan Kettering-Memorial group, 60 per cent had pain presumed to be due to viral burden or immunosuppression, 30 per cent had pain due to antiviral treatment, and 10 per cent had pain caused by chronic non-HIV-related conditions. Neuropathic pain syndromes in AIDS are common.

About 30 per cent of patients develop the so-called peripheral neuropathy of HIV that characteristically presents as symmetrical distal burning, numbness, and pins-and-needles sensation.

Another 10 per cent may develop myelopathy from viral infection of the spinal cord. Other causes of neuropathic pain in AIDS patients include immune-mediated neuropathy, toxic neuropathies (e.g., due to alcohol), nutritional deficiencies (e.g.. folate and B1Z), antiretroviral therapy (e.g.,ddI, ddC), chemotherapy (e.g., vineristine), radiotherapy, surgery, and treatment with phenytoin (Dilantin) or isoniazid (INH).

As emphasized above, CD4 cell values less than 200 per mm' raise the index of suspicion for more serious causes.

Therapy of pain in HIV/AIDS broadly follows the WHO method for cancer pain relief

When the predominant pain in an individual is noeiceptive, therapy should begin according to the WHO ladder with a nonopioid such as paracetamol, then progress as needed to co-administer a weak (or if that is inadequate, a strong) opioid.

Because of marrow depression from HIV disease or antiviral drugs, and widespread GI complaints seen with HIV/AIDS, the use of nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase-1 is generally discouraged.

Paracetamol (=acetaminophen in North America), a cyclooxygenase-3 inhibitor, is used when available, with awareness that hepatic comorbidity and malnutrition predispose to paracetamol toxicity.

Progression up the "ladder" to incorporate an opioid is the next step, although this is often not possible in practice because of the unavailability of opioids in many settings. Through ongoing efforts, WHO is addressing the need to optimise, and achieving balance in, national opioid policies.

Opioids are efficacious for nociceptive and neuropathic pain although the degree of responsiveness of the latter is in general less complete than the former. In the presence of AIDS dementia, opioids must be titrated cautiously and co administered when possible with agents that are opioid dose-sparing (e.g., paracetamol) or that counteract opioid-induced sedation.

Known or suspected substance abusers should not be denied appropriate pharmacotherapy, and the label of "substance abuser" should be applied cautiously. When the suspicion of ongoing substance abuse is high, effective pain management can be achieved by setting clear goals and conditions for maintainins therapy, that make consequences of aberrant use clear.

Written or oral agreements between patient and clinician can establish a single provider, and make the consequences of aberrant use explicit from the start of therapy.

At any stage of painful HIV/AIDS. adjuvant therapies either to augment opioid analgesia or as analgesics in their own right against neuropathic pain, are often appropriate.

Such adjuvants include tricvclic antidepressants (whose side effect of constipation, shared with opioids, is often useful in diminishing the symptom of diarrhea) and anticonvulsants. Anticonvulsants with a high potential to depress the bone marrow, such as phenytoin, are usually avoided.

Conclusion :
Pain in HIV/AIDS can and must be controlled

Even when an individual's condition is not reversible, palliative care and pain control improve quality of life and augment quality-adjusted life years. Examples include cancer, advanced musculoske.letal or neurological disease, traumatic amputation, postherpetic neuralgia, and so on.

The same is true for HIV/AIDS, for which economic projections indicate that global undertreatment of persons with the underlying condition, particularly in developing nations, will continue for some time. Given their relative low cost, efforts to provide palliative care, particularly pain control, are essential in all countries that share the goal of sustaining the highest possible health status for those with HIV/AIDS.

Efforts to control pain and other symptoms in HIV/AIDS must provide ongoing evaluation of pain and other symptom intensity, relief, mood state or psychological distress, and adverse drug effects including side effects, misuse and abuse.

Submitted By
Dr. Daniel b. Carr, Md

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