Nausea and vomiting in HIV: a symptom review

Abstract

Nausea and vomiting are two of the most common symptoms experienced by those with HIV. While the causes are most commonly attributed to medication side effects, infectious causes, gastroparesis and psychosomatic, therapy aimed at controlling symptoms has not been well studied. Since nausea and vomiting have been identified as the most common cause of discontinuation of highly active antiretroviral therapy (HAART) therapy, and due to the extensive morbidity associated with these symptoms, we sought to review and discuss causes and management of these symptoms in HIV-infected patients and demonstrate the need for further research in this area. Such studies could include investigation into the prophylactic use of antiemetics with initiation or modification of HAART therapy to monitor patient compliance. In addition, anticipatory nausea and vomiting should be further studied, as it could prove to be quite prevalent, as in cancer patients.

Keywords

highly active antiretroviral therapy nausea vomiting

INTRODUCTION

Nausea and vomiting are among the most frequently encountered symptoms experienced by those with HIV.¹ At some point of their illness, almost everyone with HIV/AIDS will experience these symptoms that can often be severe. While these symptoms are extremely common, the aetiology in many cases is unclear and has not been well studied in HIV research. The purpose of this article is to review and discuss causes and management of nausea and vomiting in the HIV population and the need for research in this area.

Nausea and vomiting have been reported as one of the 12 most frequent and bothersome symptoms in patients with HIV.¹ The differential is broad, and major causes in HIV include drug-induced, infectious, gastroparesis, psychological or any combination. Symptoms can be severe enough to cause discontinuation of antiretroviral medications, causing further progression of the disease, leading to further physical and psychological discomfort. According to a recent report, nausea was the most frequently cited prompt for highly active antiretroviral therapy (HAART) discontinuation, responsible for 27% of those terminating therapy secondary to an adverse event.²

DEFINING NAUSEA AND VOMITING

Nausea is a subjective sensation that is associated with the urge to vomit. It is a conscious awareness of the stimulation of the vomiting centre. Causes are diverse and include foods, drugs, toxins, motion sickness, pregnancy, endocrine disorders and neurological diseases.³ Physical manifestations include pallor, tachycardia and diaphoresis.³

Vomiting, which is the forceful discharge of gastric contents through the mouth, is often, but not always associated with nausea. It is caused by stimulation of the vomiting centre, capable of receiving stimulation from multiple sources. Manifestations include salivation, shivering and vasomotor changes.³

Nausea and vomiting can be protective when they signal a disease process through which vomiting removes the noxious agent(s).³ However, they can be problematic when they impair nutritional status and lead to a loss of fluids and nutrients. As mentioned above, they can also interfere with adherence to necessary medications.

PATHOPHYSIOLOGY OF NAUSEA AND VOMITING

The pathways involved in stimulating vomiting are well defined. An understanding of the neural pathways involved in nausea and vomiting can provide a foundation for approaching and managing these symptoms. The vomiting centre, located in the lateral medullary reticular formation of the central nervous system (CNS) coordinates emesis and can be activated in a number of different ways including the gastrointestinal (GI) tract, the vestibular apparatus and the chemoreceptor trigger zone (CTZ).³

Afferent nerves to the vomiting centre arise in the GI tract, which communicate through the solitary tract nucleus (STN) of the vagus nerve, and also through the abdominal splanchnic nerves via the spinal cord.³ These fibres sense both mechanical and chemical change, including contraction and distension of the gut, physical damage, intestinal obstruction and gastric distention caused by stasis.³ The information is then relayed to the CTZ, which lies in the area postrema of the fourth ventricle.³ Here, due to the lack of the blood–brain barrier, chemoreceptors can also detect stimuli of endogenous origin such as hormones associated with pregnancy, and also of exogenous origin such as toxins or drugs from the rich blood supply and cerebrospinal fluid that it is surrounded by.³ Two other important inputs to the CTZ are the cerebral cortex (particularly involved in anticipatory nausea or vomiting discussed below) and the vestibular apparatus (in motion sickness).³

The CTZ is directly linked with the emetic centre located within the medulla.³ Once activated, a complex coordinated set of muscular contractions, cardiovascular responses and reverse peristalsis ensues as a result of the efferent branches of cranial nerves V, VII, IX and X, that characterizes vomiting.³

Studies have shown that the CTZ is rich in dopamine (D2), serotonin (5-HT3), neurokinin 1 (NK1) and opioid receptors.³ Thus, the CTZ has remained a target for medical therapy.

PREVALENCE OF NAUSEA AND VOMITING IN HIV

The prevalence of nausea and vomiting in HIV patients was described in 2005.¹ Nausea was found in approximately 50% of patients, with over half admitting to severe and persistent nausea.¹ In addition, close to 60% were receiving treatment for their symptoms. The prevalence of vomiting was found to be approximately 25%, one-third of which admitting to severe and persistent vomiting. Approximately two-thirds of those patients were receiving treatment.¹

CAUSES OF NAUSEA AND VOMITING

The causes of nausea and vomiting in HIV are vast. Symptoms can be attributed to medications, infection, gastroparesis and psychosomatic, or any combination of the above.

MEDICATION SIDE EFFECTS

Antiretrovirals (ARVs) are the most common cause of HIV-associated nausea and vomiting.⁴ A recent study found that 46% of prescribed medications in the treatment of HIV have nausea and vomiting listed as an adverse effect.⁵ It is often quite difficult to identify which agent(s) are responsible for such symptoms, especially when multidrug regimens are started. ARVs that are notorious for inducing nausea and vomiting include nevirapine (20–38%), amprenavir, ritonavir (10%), efavarenz and abacavir.⁴ While nausea and vomiting most frequently occur at the start of therapy, they may persist throughout the course of therapy.⁶ In addition, chemotherapeutic agents involved in the treatment of HIV-related malignancies such as Kaposi's sarcoma and lymphomas have also been known to stimulate the vomiting centre.⁷ Such agents include bleomycin, cyclophosphamide, doxorubicin, etoposide, ifosfamide, methotrexate, vinblastine and vincristine.⁸ Of note, liposomal doxorubicin, used to treat Kaposi's sarcoma, has been particularly implicated in causing severe nausea and vomiting.⁹

While some believe that ARVs directly irritate the lining of the GI tract, some studies suggest that these side effects are a result of the body regarding the medications as toxins and attempting to eliminate them.¹⁰ Currently all non-nucleoside reverse transcriptase inhibitors and all protease inhibitors are known to cause nausea, vomiting or GI upset.⁵ The occurrence and severity of such symptoms vary widely among individuals, however toxic side effects are seen more frequently in those with advanced disease.⁴ A possible explanation could be the need for multiple medications to treat those with more advanced disease, increasing the likelihood of symptoms secondary to medications.

Table 1 lists the various drugs that have been known to cause nausea and vomiting in HIV patients. Drugs used to treat comorbid conditions associated with HIV also produce GI symptoms. Examples include cidofovir, foscarnet and ganciclovir, all used to treat cytomegalovirus (CMV); antifungals such as fluconazole, ketoconazole (nizoral) and itraconazole; interferon alpha, used for chronic hepatitis B and C; and antimycobacterial agents such as rifampin and ribafutin.⁵ As mentioned above, most chemotherapeutic agents also cause nausea by targeting rapidly growing cells, including those lining the stomach.⁸

Table 1

Medications commonly prescribed in HIV/AIDS associated with nausea/vomiting

Chemical name	Trade (common) name	Class
Abacavir	Ziagen	NRTI
Acyclovir	Zovirax	Antiviral
Amithiozone	Tibione	Antitubercular
Amphotericin B	Amphocin/Fungizone	Antifungal
Amprenavir	Agenerase	Protease Inhibitor
Atazanavir	Reyataz	Protease Inhibitor
Atovaquone	Mepron	Antiprotozoal
Azithromycin	Zithromax	Antibiotic – Macrolide
Cidofovir	Vistide	Antiviral
Ciprofloxacin	Cipro	Antibiotic – Fluoroquinolone
Clarithromycin	Biaxin	Antibiotic – Macrolide
Clindamycin	Cleocin	Antibiotic – Lincosamide
Dapsone	Dapsone	Leprostatic
Delavirdine	Rescriptor	NNRTI
Didanosine	Videx	NRTI
Efavirenz	Sustiva	NNRTI
Famciclovir	Famvir	Antiviral
Fluconazole	Diflucan	Antifungal
Flucytosine	Ancobon	Antifungal
Fosamprenavir	Lexiva	Protease Inhibitor
Foscarnet	Foscavir	Antiviral
Ganciclovir	Cytovene	Antiviral
Indinavir Sulfate	Crixivan	Protease Inhibitor
Iodoquinol	Yodoxin	Amebicide
Itraconazole	Sporanox	Antifungal
Ketovonazole	Nizoral	Antifungal
Lamivudine	Epivir	NRTI
Lopinavir	Kaletra	Protease Inhibitor
Metronidazole	Flagyl	Antibiotic
Nelfinavir	Viracept	Protease Inhibitor
Nevirapine	Viramune	NNRTI
Ofloxacin	Floxin	Antibiotic – Fluoroquinolone
Paromomycin	Humatin	Antibiotic – Aminoglycoside
Pentamidine	Pentam	Antiprotozoal
Pyrimethamine	Daraprim	Antimalarial
Rifabutin	Mycobutin	Antitubercular
Ritonavir	Norvir	Protease Inhibitor
Saquinavir	Invirase	Protease Inhibitor
Stavudine	Zerit	NRTI
Tenofovir	Viread	NRTI
TMP/SMZ	Bactrim	Antibiotic
Zidovudine	Retrovir	NRTI

Source: Table adapted with information from Goodman & Gilman's the pharmacological basis of therapeutics (2006)

NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = Non-nucleoside reverse transcriptase inhibitor

INFECTIOUS

Infectious aetiology is another primary cause of nausea and vomiting in HIV patients. Table 2 highlights the wide variety of microorganisms that can cause GI symptoms. Those with late-stage HIV and compromised immune status are susceptible to opportunistic pathogens, which have dramatically decreased since the widespread use of effective combination antiretroviral therapy.⁴ Such infections include Cryptosporidium parvum, herpes simplex virus (HSV), CMV, Mycobacterium avium-intracellularae (MAI) and gut involvement of Kaposi's sarcoma.⁴ Cryptosporidiosis, transmitted through contaminated food and water, usually characterized by abdominal cramps, diarrhoea and wasting, can also involve the stomach and upper GI tract, leading to nausea and vomiting.⁴ It can also involve the biliary tree leading to nausea and vomiting.⁴ HSV and CMV should be suspected in any patient with a history of oral ulcers.

Table 2

Common gastrointestinal pathogens causing nausea and vomiting

Bacteria	Protozoans	Viruses	Fungi
Campylobacter jejuni	Blastocystic hominis	Adenovirus	Candida spp.
Clostridium difficile	Cryptosporidium parvum	Astrovirus	Histoplasma capsulatum
Escherichia coli	Cyclospora cavetanensis	Calcivirus
Listeria monocytogenes	Encephalitozoon intestinalis	Cytomegalovirus
Mycobacterium avium	Entamoeba histolytica	Norwalk virus
Mycobacterium intracellulare	Enterocytozoon bieneusi	Picobirnavirus
Salmonella spp.	Giardia lamblia	Rotavirus
Shigella spp.	Isospora belli
Staphylococcus aureus
Vibrio cholerae and V. parahaemolyitcus

Source: Table adapted with information from Highleyman (2002)

CNS disturbances should also be ruled out in those with unexplained nausea and vomiting. Toxoplasmosis and meningitis can both lead to increased intracranial pressure, which has been associated with nausea and vomiting.

Endocrine dysfunction has also been noted as a result of opportunistic infections.¹¹ Such pathogens include CMV, cryptococcus, toxoplasma, mycobacteria and candida. These pathogens primarily induce adrenal insufficiency and pancreatic dysfunction. Thus, in any patient with electrolyte abnormalities associated with nausea and vomiting, adrenal disease must be entertained, specifically those in which Kaposi's sarcoma is possible.¹¹ Similarly, in those patients presenting with nausea, vomiting and abdominal pain, pancreatic disease should be ruled out.

GASTROPARESIS

Gastroparesis should be considered as aetiology in HIV patients who report early satiety or vomit undigested food more than two hours after a meal. Visceral neuropathy secondary to HIV infection was first described by Konturek et al. in 1997.¹² Konturek et al. studied gastric motor activity in 20 HIV-positive men and women with abdominal complaints of dyspepsia, dysphagia, nausea, vomiting, diarrhoea and postprandial fullness. A significant delay in gastric emptying of solids and accelerated emptying of fluids, in addition to diminished postprandial antral motility was found, suggestive of a possible autonomic neuropathy. Thus, a cause of the persistent symptoms was thought to have been found. Subjects, however, were not screened for the presence of enteric infections, nor were correlations made to stage of HIV infection or weight loss.

Follow-up revealed that the gastric emptying rate was significantly delayed in HIV-infected subjects, particularly those with enteric infections and more advanced disease, although the cause remains unexplained.¹³ Such enteric infections include cryptosporidial and CMV infection.^14,15 Enteric opportunistic infections become more common with increasing immunosuppression, and such infections have been associated, in non-HIV-infected populations, both with gastric motor abnormalities and small intestinal dysmotility, which could lead to functional gastric outflow obstruction.¹³

While damage to the autonomic division was previously thought to contribute to GI dysfunction in HIV disease, Penny et al. ¹³ found that there was no correlation between gastric symptoms and autonomic dysfunction leading to impairment of gastric emptying. Their study found that although solid gastric emptying was significantly delayed in HIV patients from a delayed rate of emptying, there was no correlation to actual symptomatology. This suggests our understanding regarding gastric motor function and its relation to upper GI symptoms is incomplete.

PSYCHOLOGICAL

Psychological factors also may contribute to nausea and vomiting experienced by HIV patients. Anticipatory nausea and vomiting (ANV) is a phenomenon in which a response exists to various stimuli such as odours, tastes, experiences and objects.¹⁶ ANV well described in cancer patients prior to receiving chemotherapy, however has not been studied in HIV disease. A Pavlovian conditioned reflex, where the conditioned stimulus (CS) is the thought of chemotherapy or of elements associated with it. When patients are re-exposed to the CS, some patients will then experience ANV prior to infusion onset.¹⁷ Prior experience of nausea and vomiting associated with the CS, however, is not always necessary.

Once ANV develops, it is difficult to control pharmacologically.¹⁷ The best method to avoid development or reinforcement of ANV is to avoid both nausea and vomiting from the first exposure.¹⁷ Preventing food aversions during nausea and vomiting is also a form of prevention. Patients may associate certain foods with nausea and vomiting that will perpetuate their symptoms. Experimental animal settings have shown that effective strategies to alleviate nausea and vomiting could include certain conditioning techniques.^18,19 Behavioural therapies involving relaxation, notably systematic desensitization have also been shown to effectively control ANV in adult and paediatric cancer patients undergoing chemotherapy.²⁰ If pharmacological measures are to be used, benzodiazepines, specifically alprazolam, have been documented to help in adult patients.²¹ While ANV has not been studied in HIV research, the above strategies have been recommended for patients with HIV suffering from nausea and vomiting.²²

MANAGEMENT

The first step in management of nausea and vomiting in an HIV patient is to determine the underlying cause. This usually entails an investigation as to whether a relationship exists between onset of symptoms and initiation of any medication, usually an ARV, in which case dietary modifications may help.⁴ For example, eating high-fat foods such as peanut butter, prior to taking ritonavir, may improve nausea.⁴ Another option would be to change the antiviral medication or to eliminate all non-essential medications. While switching the initial HAART regimen due to intolerance does limit further treatment options, discontinuing medication is hazardous and would promote resistance and worsened viremia.² Thus, cases in which adherence may become an issue, changing the HAART regimen is a reasonable option. If caused by a pathogen, treating the underlying infection usually resolves symptoms. Therefore, if a pathogen is suspected, symptomatic treatment should not be started immediately in order to monitor the infectious course and allow the body to rid itself of the infection.

Pharmacological management is listed in Table 3. Serotonin receptor antagonists are highly effective with few side effects. They work by selectively binding 5-HT3 receptors in the CTZ and also through blockade of peripheral 5-HT3 receptors in extrinsic intestinal vagal and spinal afferent nerves.³ They have been classified as having the highest antiemetic therapeutic index by The American Society of Clinical Oncology.²³ The serotonin antagonists have been shown to be particularly effective in preventing chemotherapy-induced nausea and vomiting; however, they are used in other settings such as postoperative nausea due to vagal stimulation.³ These agents do not inhibit dopamine or muscarinic receptors, nor do they have effects on oesophageal or gastric motility.³

Table 3

Symptomatic treatment of HIV/AIDS-related nausea/vomiting

Class	Chemical name	Trade name	Regimen
Anticholinergic	Hyoscine	Scopolamine	1.5 mg transdermal patch q3 days
Antihistamines	Diphenhydramine	Benadryl	25–50 mg q4–6 hours
	Hydroxyzine	Vistaril	25–10 mg q6–8 hours
	Meclizine	Antivert	25–100 mg q12 hours
Benzodiazepines	Lorazepam	Ativan	0.5–2.0 mg PO q4–6 hours, maximum 4 mg/day
Butyrophenones	Droperidol	Inapsine	2.5–5 mg i.m. or i.v. q6–8 hours
Butyrophenones	Haloperidol	Haldol	0.5–5.0 mg q6–12 hours PO or i.m.
Cannabinoids	Dronabinol	Marinol	2.5 mg PO b.i.d., if tolerated, may increase to 10–20 mg/day
Cannabinoids		Marijuana	Medicinal use legal only in CA and AZ
Glucocorticoids	Dexamethasone	Decadron	4–12 mg/day q6–8 hours
Phenothiazines	Prochlorperzine	Compazine	5–10 mg PO q6–8 hours, 25 mg PR b.i.d., 5–10 mg i.m. q4
Phenothiazines	Promethazine	Phenergan	12.5–25 mg PO, PR or i.m. q4–6 hours
Serotonin	Ondansetron	Zofran	4–8 mg PO or i.v. q8–12 hours
Antagonists	Granisetron	Kytril	1–2 mg PO or 10 mg/kg i.v.
	Dolasetron	Anzemet	q12 hours
	Palonosetron	Aloxi	50–100 mg PO or 12.5–100 mg i.v. daily
			0.25 mg i.v. (1/2 life of 40 hours)
Substituted	Metoclopramide	Reglan	5–10 mg q4–6 hours i.v., PO, or SC
Benzamides	Trimethobenzamide	Benzacot	250 mg PO, 200 mg PR/i.m.

Source: Table adapted with information from Goodman & Gilman's the pharmacological basis of therapeutics (2006)

Substituted benzamides are dopamine antagonists, of which metoclopramide (reglan) is considered the prototypical medication. In addition to antiemetic effects, reglan has substantial peripheral cholinergic effects that enhance gastric emptying.²² Therefore, it is particularly useful in treating gastroparesis/GI motility disorders.³ The effectiveness is limited by side effects which include acute dystonic reactions, akathisia and sedation.

Butyrophenones which include haloperidol, and phenothiazines such as prochlorperzine are also antidopaminergic agents with antiemetic activity. They act by inhibiting cerebral dopamine receptors at the CTZ. Efficacy rates are usually lower than that of reglan. Adverse effects include sedation, akathisia, dystonic reactions and orthostatic hypotension.²³ Caution should be taken with the above medications, as extrapyramidal side effects may be more pronounced in patients with AIDS in comparison to others suffering from nausea.²²

Cannabinoids such as marinol exert effects via the CNS through a mechanism not well understood. They have been found to have antiemetic effects when used alone or in conjunction with other medications.³ It has been Food and Drug Administration (FDA) approved only for use as an appetite stimulant in AIDS patients, though it has been used for management of antiretroviral associated nausea and vomiting in HIV/AIDS patients, despite the absence of published clinical effectiveness.²⁴ While only legal in California and Arizona, a recent study showed use of smoked marijuana specifically for amelioration of nausea may be associated with increased adherence to ARVs among patients with HIV/AIDS.²⁵

Antihistamines and anticholinergics are useful in controlling nausea and vomiting resulting from motion sickness or inner ear disturbances. They do not act on the CTZ and are thus of little value in other causes of vomiting.³ They can however be used in patients on phenothiazines or other antidopaminergic medications such as reglan, since they will usually prevent dystonic reactions.³ H2-antagonists or proton pump inhibitors can be used if gastritis/gastro-oesophageal reflux disease (GERD) are suspected as causes of nausea and vomiting. Benzodiazepines are used prior to initiation of chemotherapy to reduce ANV, as mentioned above.³ Corticosteroids are useful in selected refractory cases of nausea and vomiting, although the overall utility of steroid therapy in HIV patients depends on possible immunosuppressive effects.⁴

Dietary interventions such as eating smaller, low fat, bland, more frequent meals potentially, although unproven, can alleviate gastroparetic symptoms.⁴ Antiemetics can be used parenterally or by suppository if the patient is unable to take oral medications. If symptoms are refractory or chronic, around the clock antiemetic administration should be considered. Relaxation techniques such as progressive muscle relaxation training (PMRT) and guided imagery have also been effective in chemotherapy-induced nausea and vomiting,²⁶ and thus may be useful in HIV-associated disease. Acupuncture, acupressure and emotional support are reasonable, although unproven alternative therapies.

If the above measures fail, diagnostic testing to identify treatable disorders should be pursued. A reasonable first step would be to perform an upper endoscopy to rule out active oesophagitis, either from GERD or opportunistic infections, and also to rule out structural abnormalities of the upper GI tract.⁴ A gastric emptying study could also be performed to rule out gastroparesis. Imaging studies of the brain are also appropriate to rule out space-occupying CNS lesions if focal neurological deficits are present. If all workup is negative, psychological evaluation could reveal a primary mood disturbance, aversions or anticipatory symptoms. Further therapy should be directed based on the results of these studies.

DISCUSSION

GI symptoms are common in HIV patients, particularly those with advanced disease.²⁷ Nausea and vomiting are clinical issues that affect approximately 50% of HIV patients.⁴ Although such symptoms are often thought to be secondary to medication side effects, infectious causes or gastroparesis, often times such symptoms are extensively investigated, without a cause becoming apparent.¹³

Due to the extensive morbidity nausea and vomiting can cause, leading to malnutrition, non-adherence to medications and detrimental quality of life, and because of the frequent unexplained causes, the authors suggest further research be directed towards studying these symptoms in the HIV population. A study at UCSF found that concern over side effects was a major factor deterring people from starting antiretroviral treatment.¹⁰ We feel that investigating the effectiveness of known drug therapies and developing new therapies are important measures that could improve patient outcome. Adverse effects of ARVs leading to non-adherence have led to an increasing incidence of viral resistance and cross-resistance when ARVs are abruptly started and stopped²⁸ In addition, switching from the initial HAART regimen results in a lower probability of virological suppression and frequent switching may exhaust future options for effective treatment.² Therefore, appropriate prophylaxes may be warranted in order to increase the likelihood of adherence to the prescribed regimen. As with ANV, the best method of management may be to avoid nausea and vomiting before they begin.

While numerous studies have been conducted regarding management in cancer patients, pregnancy and postoperative emetic patients, only one study was found regarding the symptom management of nausea and vomiting in HIV disease. A small-scale study evaluating the efficacy of zofran for patients on high-dose bactrim for Pneumocystis carinii pneumonia (PCP) was conducted by Gompels et al. in 1993.²⁹ The results indicated that 50% (8 of 16) experienced less vomiting during PCP treatment with zofran. While GI symptoms including nausea and vomiting have been found at levels similar to those reported for cancer patients,³⁰ management could prove to be quite different. Efficacy rates and patient utilization in pharmacological management of nausea and vomiting in HIV disease were not found in reviewing the literature. Therefore, current management is based on studies performed on cancer patients, personal preference, expert opinion and individual symptomatic improvement.

While expert opinion often time points to gastroparesis as a cause of symptoms in patients with advanced HIV disease, studies have not confirmed this. Despite the fact that gastroparesis is a known entity in advanced HIV disease, there has not been direct correlation to symptoms. While reglan is often times prescribed for those with gastroparetic like symptoms, perhaps the improvement in symptoms is secondary to its dopamine antagonist properties. The authors suggest that further studies be conducted in order to better characterize the significance of gastroparesis and its relation to HIV-related GI symptoms.

With regards to ANV, while this cause has been studied extensively in cancer patients, it has not been adequately researched in HIV populations. The high rate of severe nausea and vomiting, often requiring multiple medications, suggests our understanding of these symptoms in HIV patients is not fully understood. We suggest that cases that are refractory to treatment, and in which no other cause can be identified, that ANV be considered. It is plausible that ARVs become the CS, where each time a patient ingests their medication, they become nauseous, perpetuating a cycle. Further studies could reveal ANV or other psychological disturbances to be a major cause of nausea and vomiting in HIV patients. Assessment as to whether alprazolam is effective in controlling ANV in those patients in which it is suspected should also be considered.

Initial studies are needed to investigate the overall scope of nausea and vomiting and its relationship to medications, nutritional status and psychological wellbeing. The low proportions of patients who reported therapy for symptoms with known treatments, such as nausea and vomiting, calls for improvements in education among general medical staff and indicate a need for a more skilled palliative assessment and management.¹ Interviews could be conducted to better understand the causes and their effects on patients overall state. Also, prescribed medications and their effectiveness could be documented to gain a better understanding of which interventions are most beneficial, specifically with relation to multidrug regimens. For example, serotonin antagonists with corticosteroids, which have been proven to have improved efficacy for highly emetogenic chemotherapeutic regimens.³

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