Complications Associated with HIV/AIDS Patients || Pharmacyteach.com

 Complications Associated with HIV/AIDS Patients

 

A. Systemic Complaints

Fever, night sweats, and weight loss are frequently observed symptoms in patients infected with HIV and may manifest in the absence of a complicating opportunistic infection.

Patients experiencing persistent fever without any localizing symptoms should still undergo a thorough examination and be assessed with a chest radiograph (Pneumocystis pneumonia can occur without respiratory symptoms), bacterial blood cultures if the fever exceeds 38.5°C, serum cryptococcal antigen testing, and mycobacterial blood cultures.

To investigate potential occult sinusitis, Sinus CT scans or sinus radiographs should be considered. If these examinations yield normal results, patients should be monitored closely. Antipyretics can be beneficial in preventing dehydration.

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1. Weight loss and wasting syndrome:

Weight loss is a particularly distressing complication of long-standing HIV infection. Patients typically have disproportionate loss of muscle mass, with maintenance or less substantial loss of fat stores. The mechanism of HIV-related weight loss is not completely understood but appears to be multifactorial.

 

A.   PRESENTATION-

Individuals diagnosed with AIDS often experience anorexia, nausea, and vomiting, all of which lead to reduced weight by lowering caloric consumption. In certain instances, these symptoms may be a result of a specific infection, such as viral hepatitis. However, in other situations, an assessment of the symptoms does not reveal any particular pathogen, leading to the assumption that they are a primary effect of HIV. Additionally, malabsorption contributes to the reduction in caloric intake. Patients may also experience diarrhea due to infections caused by bacterial, viral, or parasitic agents.

 

Compounding the reduction in caloric intake, numerous AIDS patients exhibit an elevated metabolic rate. This heightened rate has been observed even in asymptomatic individuals infected with HIV, but it intensifies as the disease progresses and with the onset of secondary infections. AIDS patients suffering from secondary infections also experience diminished protein synthesis, which complicates the preservation of muscle mass.

 

B.   MANAGEMENT-

Multiple approaches have been established to mitigate AIDS wasting. In the long run, antiretroviral therapy (ART) remains the most effective option, as it addresses the root cause of the HIV infection. In the short term, managing fever effectively can lower the metabolic rate and potentially reduce the rate of weight loss, similar to the treatment of any underlying opportunistic infections. Providing high-calorie drinks as food supplementation may assist patients with diminished appetite in sustaining their nutritional intake. Certain patients who maintain good functional status but experience weight loss due to persistent nausea, vomiting, or diarrhea might find total parenteral nutrition (TPN) beneficial. It is important to highlight, however, that TPN is more inclined to enhance fat reserves rather than reverse the process of muscle wasting.

Medical Approaches to Appetite and Weight Management in HIV Patients:

Two pharmacological methods to enhance appetite and promote weight gain include the progestational agent megestrol acetate (80 mg taken orally four times daily) and the antiemetic agent dronabinol (2.5-5 mg taken orally three times daily); however, neither of these medications contributes to an increase in lean body mass.

Although side effects from megestrol acetate are infrequent, instances of thromboembolic events, edema, nausea, vomiting, and rash have been documented. In the case of dantrolene, side effects such as euphoria, dizziness, paranoia, somnolence, and even nausea and vomiting have been observed in 3-10% of patients.

Dronabinol contains only one of the active components found in marijuana, and numerous patients have reported experiencing greater relief from nausea and enhanced appetite when using medical cannabis, which can be administered through smoking, vaporization, essential oils, or incorporation into food. In the United States, a minimum of 23 states, along with the District of Columbia, permit patients to access marijuana for medical purposes, provided they have a recommendation letter from their physician. Nonetheless, the use and distribution of marijuana remain illegal under federal law.

Two treatment protocols that have led to increases in lean body mass include growth hormone and anabolic steroids. Administering growth hormone at a dosage of 0.1 mg/kg/day (up to 6 mg) via subcutaneous injection for 12 weeks has been shown to produce modest gains in lean body mass. The expense of growth hormone treatment can reach as high as $10,000 monthly. Anabolic steroids are also effective in enhancing lean body mass in patients infected with HIV. Their efficacy appears to be maximized in individuals who engage in weight training. The most frequently utilized regimens consist of testosterone enanthate or testosterone cypionate (100-200 mg administered intramuscularly every 2-4 weeks). Additionally, the testosterone transdermal system (5 mg applied each evening) and testosterone gel (1%; applying a 5-g packet [50 mg testosterone] to clean, dry skin daily) are also options. Furthermore, the anabolic steroid oxandrolone (20 mg taken orally in two divided doses) has been shown to promote increases in lean body mass.

 

2. Nausea that results in weight loss can sometimes be attributed to esophageal candidiasis. Patients experiencing oral candidiasis along with nausea should receive empirical treatment with an oral antifungal medication. Individuals who experience weight loss due to nausea of an unknown cause may find relief through the use of antiemetics before meals (prochlorperazine, 10 mg three times a day; metoclopramide, 10 mg three times a day; or ondansetron, 8 mg three times a day). Dronabinol (5 mg three times a day) or medical cannabis may also be effective in alleviating nausea.

Depression and adrenal insufficiency are two potentially treatable factors contributing to weight loss.

 

B. Pulmonary Disease

1. Pneumocystis pneumonia:

P jirovecii pneumonia represents the most prevalent opportunistic infection linked to AIDS. Diagnosing Pneumocystis pneumonia can be challenging due to the nonspecific nature of its symptoms, which include fever, cough, and shortness of breath. Additionally, the severity of these symptoms can vary, ranging from fever without respiratory symptoms to mild cough or dyspnea, and even to significant respiratory distress.

Hypoxemia can be quite severe, with a PO2 level falling below 60 mm Hg. The primary method for diagnosis is through a chest radiograph.

Diffuse or peripheral infiltrates are the most typical findings; however, only about two-thirds of patients with Pneumocystis pneumonia exhibit this characteristic. Normal chest radiographs are observed in 5-10% of patients diagnosed with Pneumocystis pneumonia, while the rest display atypical infiltrates. Patients undergoing aerosolized pentamidine prophylaxis often present with apical infiltrates. It is rare for large pleural effusions to occur in Pneumocystis pneumonia; their presence may indicate bacterial pneumonia, other infections such as tuberculosis, or pleural Kaposi sarcoma.

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A definitive diagnosis can be achieved in 50-80% of instances through the use of Wright-Giemsa stain or the direct fluorescence antibody (DFA) test on induced sputum. Sputum induction is carried out by having patients inhale an aerosolized solution of 3% saline generated by an ultrasonic nebulizer. Patients are advised not to consume food for at least 8 hours and to refrain from using toothpaste or mouthwash before the procedure, as these can affect the interpretation of the test. The next step for patients with negative sputum examinations in whom Pneumocystis pneumonia is still suspected should be bronchoalveolar lavage. This technique establishes the diagnosis in over 95% of cases.

In patients exhibiting symptoms indicative of Pneumocystis pneumonia, yet presenting with negative or atypical chest radiographs and negative sputum tests, alternative diagnostic assessments may yield further insights to determine the necessity of proceeding with bronchoalveolar lavage. The elevation of serum lactate dehydrogenase is observed in 95% of Pneumocystis pneumonia cases; however, the specificity of this result is, at most, 75%.

 

In contrast, a serum betaglucan test offers greater sensitivity and specificity for Pneumocystis pneumonia compared to serum lactate dehydrogenase, potentially allowing for the avoidance of more invasive procedures when applied in a suitable clinical context.

A normal diffusing capacity of carbon monoxide (DLC) or a high-resolution CT scan of the chest that shows no interstitial lung disease renders the diagnosis of Pneumocystis pneumonia highly improbable. Furthermore, a CD4 count exceeding 250 cells/mcl. Within two months before the assessment of respiratory symptoms also makes the diagnosis of Pneumocystis pneumonia becomes unlikely; only 1-5% of cases occur at this CD4 count level (Figure 31-1). This holds true even if the patient had a previous CD4 count below 200 cells/mcL. But has experienced an increase due to ART.

Pneumothoraces may be observed in HIV-infected individuals with a history of Pneumocystis pneumonia, particularly if they have undergone aerosolized pentamidine treatment.

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2. Other infectious pulmonary diseases:

PRESENTATION

Other infectious agents responsible for pulmonary disease in patients with AIDS encompass bacterial, mycobacterial, and viral pneumonias. Community-acquired pneumonia stands as the predominant cause of pulmonary disease among individuals infected with HIV. There has been a reported rise in the incidence of pneumococcal pneumonia accompanied by septicemia, as well as pneumonia caused by Haemophilus influenzae. Pseudomonas aeruginosa emerges as a significant respiratory pathogen in advanced stages of the disease, and, less frequently, pneumonia resulting from Rhodococcus equi infection may occur. The rate of infection with Mycobacterium tuberculosis has significantly escalated in urban areas due to HIV infection and homelessness. Tuberculosis is estimated to affect approximately 4% of individuals in the United States who are diagnosed with AIDS.

Apical infiltrates and disseminated disease are more prevalent in individuals with compromised immune systems compared to those who are immunocompetent. It is essential to conduct a purified protein derivative (PPD) test on all individuals infected with HIV when tuberculosis is suspected; however, a lower CD4 cell count correlates with an increased risk of allergy. Due to the inability of 'allergy' skin test panels to accurately identify patients who are infected with tuberculosis yet show no reaction to the PPD, their use is not advised. Interferon gamma release assays, such as the QuantiFERON and T-SPOT tests, are expected to demonstrate greater sensitivity than skin testing in HIV-infected individuals suspected of having tuberculosis.

 

B. MANAGEMENT:

The treatment approach for individuals with HIV who also have active tuberculosis is akin to that for those without HIV who have tuberculosis. Nevertheless, rifampin should not be administered to patients who are on a boosted protease inhibitor (PI) regimen. In such instances, rifabutin may be used as a substitute, although it may necessitate adjustments in dosing based on the specific antiretroviral regimen. The emergence of multidrug-resistant tuberculosis has become a significant issue in various metropolitan regions of the developed world, and the reports from South Africa regarding 'extremely resistant' tuberculosis in AIDS patients are raising global alarm. No adherence to prescribed antituberculous treatments is a critical risk factor. Many of the documented outbreaks seem to suggest a nosocomial transmission.

The rise of medication resistance necessitates that antibiotic sensitivity testing be conducted on all positive cultures. Therapeutic approaches should be tailored to the individual patient. Individuals infected with multidrug-resistant M tuberculosis should be administered at least three medications that their specific strain is sensitive to.

Atypical mycobacteria may lead to pulmonary disease in AIDS patients, regardless of any preexisting lung conditions, and their response to treatment can vary. Differentiating between M tuberculosis and atypical mycobacteria requires the culture of sputum samples. If the sputum culture reveals acid-fast bacilli, definitive identification may take several weeks when using conventional methods. DNA probes facilitate presumptive identification, typically within days of a positive culture result. While waiting for a conclusive diagnosis, healthcare providers should treat patients as if they are infected with M tuberculosis. In situations where the likelihood of atypical mycobacteria is significantly elevated (for instance, in a patient without tuberculosis exposure risk and a CD4 count below 50 cells/mcL), clinicians may choose to postpone definitive diagnosis if the patient is smear-negative for acid-fast bacilli, remains clinically stable, and does not reside in a communal environment. Isolation of cytomegalovirus (CMV) from bronchoalveolar lavage fluid occurs commonly in AIDS patients but does not establish a definitive diagnosis. Diagnosis of CMV pneumonia requires biopsy; response to treatment is poor. Histoplasmosis, coccidioidomycosis, and cryptococcal disease, as well as more common respiratory viral infections, should also be considered in the differential diagnosis of unexplained pulmonary infiltrates.

 

3. Noninfectious pulmonary diseases

 

PRESENTATION

Noninfectious causes of lung disease include Kaposi sarcoma, non-Hodgkin lymphoma, interstitial pneumonitis, and increasingly, in the current ART era, lung cancer. In patients with known Kaposi sarcoma, pulmonary involvement complicates the course in approximately one-third of cases. However, pulmonary involvement is rarely the presenting manifestation of Kaposi sarcoma. Non-Hodgkin lymphoma may involve the lung as the sole site of disease, but it more commonly involves other organs as well, especially the brain, liver, and gastrointestinal tract. Both of these processes may show nodular or diffuse parenchymal involvement, pleural effusions, and mediastinal adenopathy on chest radiographs.

 

Nonspecific interstitial pneumonitis may mimic Pneumocystis pneumonia. Lymphocytic interstitial pneumonitis, seen in lung biopsies, has a variable clinical course. Typically, these patients present with several months of mild cough and dyspnea; chest radiographs show interstitial infiltrates. Many patients with this entity undergo transbronchial biopsies in an attempt to diagnose Pneumocystis pneumonia. Instead, the tissue shows interstitial inflammation ranging from an intense lymphocytic infiltration (consistent with lymphoid interstitial pneumonitis) to a mild mononuclear inflammation.

 

MANAGEMENT

Corticosteroids may be helpful in some cases refractory to ART.

 

4. Sinusitis

 

PRESENTATION

Chronic sinusitis can be a frustrating problem for HIV-infected patients, even in those on adequate ART. Symptoms include sinus congestion and discharge, headache, and fever. Some patients may have radiographic evidence of sinus disease on a sinus CT scan or a sinus x-ray in the absence of significant symptoms.

 

MANAGEMENT

Nonsmoking patients with purulent drainage should be treated with amoxicillin (500 mg orally three times a day). Patients who smoke cigarettes should be treated with amoxicillin-potassium clavulanate (500 mg orally three times a day) to cover H influenzae. A 7-day course of pseudoephedrine 60 mg twice daily may help decrease congestion. Prolonged treatment (3-6 weeks) with an antibiotic and guaifenesin (600 mg orally twice daily) is sometimes necessary. For patients not responding to amoxicillin-potassium clavulanate, levofloxacin may be tried (400 mg orally daily). In patients with advanced immunodeficiency, Pseudomonas infections should be suspected, especially if there is no response to first-line antibiotics. Some patients may require referral to an otolaryngologist for sinus drainage.

 

C. Central Nervous System Disease

 

Central nervous system disease in HIV-infected patients can be divided into intracerebral space-occupying lesions, encephalopathy, meningitis, and spinal cord processes. Many of these complications have declined markedly in prevalence in the era of effective ART. Cognitive declines, however, may be more common in HIV patients, especially as they age (older than 50 years), even those who are taking fully suppressive ART

 

Toxoplasmosis

Toxoplasmosis is the most common space-occupying lesion in HIV-infected patients. Head-ache, focal neurologic deficits, seizures, or altered mental status may be presenting symptoms. The diagnosis is usually made presumptively based on the characteristic appearance of cerebral imaging studies in an individual known to be seropositive for Toxoplasma. Typically, toxoplasmosis appears as multiple contrast-enhancing lesions on CT scan. Lesions tend to be peripheral, with a predilection for the basal ganglia.

 

Single lesions are atypical of toxoplasmosis. When a single lesion has been detected by CT scanning, MRI scanning may reveal multiple lesions because of its greater sensitivity. If a patient has a single lesion on MRI and is neurologically stable, clinicians may pursue a 2-week empiric trial of toxoplasmosis therapy. A repeat scan should be performed at 2 weeks. If the lesion has not diminished in size, a biopsy of the lesion should be performed. A positive Toxoplasma serologic test does not confirm the diagnosis because many HIV-infected patients have detectable titers without having active disease. Conversely, less than 3% of patients with toxoplasmosis have negative titers. Therefore, negative Toxoplasma titers in an HIV-infected patient with a space-occupying lesion should be a cause for aggressively pursuing an alternative diagnosis.

 

2. Central nervous system lymphoma

Primary non-Hodgkin lymphoma is the second most common space-occupying lesion in HIV-infected patients. Symptoms are similar to those of toxoplasmosis. While imaging techniques cannot distinguish these two diseases with certainty, lymphoma is more often solitary. Other less common lesions should be suspected if there is preceding bacteremia, positive tuberculin test, fungemia, or injection drug use. These include bacterial abscesses, cryptococcomas, tuberculomas, and Nocardia lesions.

 

Management:

Stereotactic brain biopsy should be strongly considered if lesions are solitary or do not respond to toxoplasmosis treatment, especially if they are easily accessible. Diagnosis of lymphoma is important because many patients benefit from treatment (radiation therapy). Although a positive polymerase chain reaction (PCR) assay of cerebrospinal fluid for Epstein-Barr virus DNA is consistent with a diagnosis of lymphoma, the sensitivity and specificity of the test are not high enough to obviate the need for a brain biopsy.

 

3. HIV-associated dementia

Individuals diagnosed with HIV-associated dementia often experience challenges with cognitive tasks. The symptoms of dementia can fluctuate, with individuals showing alternating phases of clarity and confusion throughout the day. The diagnosis of HIV-associated dementia is made through exclusion, relying on brain imaging studies and spinal fluid analysis to rule out other pathogens. Neuropsychiatric assessments are beneficial in differentiating patients suffering from dementia from those experiencing depression. A significant number of patients show improvement with effective antiretroviral therapy (ART). Nevertheless, gradually worsening neurocognitive deficits may still arise in patients undergoing ART as they grow older.

Metabolic abnormalities may also cause changes in mental status: hypoglycemia, hyponatremia, hypoxia, and drug overdose are important considerations in this population. Other less common infectious causes of encephalopathy include progressive multifocal leukoencephalopathy, CMV, syphilis, and herpes simplex encephalitis.

 

4. Cryptococcal meningitis

Cryptococcal meningitis generally manifests with symptoms such as fever and headache. Fewer than 20% of individuals exhibit signs of meningismus. The diagnosis relies on a positive latex agglutination test of serum that identifies cryptococcal antigen (commonly referred to as "CRAG") or a positive culture of spinal fluid for Cryptococcus. Between 70% and 90% of individuals diagnosed with cryptococcal meningitis show a positive serum CRAG result. Consequently, a negative serum CRAG test renders the diagnosis of cryptococcal meningitis improbable and can be instrumental in the preliminary assessment of a patient presenting with headache, fever, and intact mental status. HIV meningitis, which is marked by lymphocytic pleocytosis in the spinal fluid alongside a negative culture, is frequently observed in the early stages of HIV infection.

5. HIV myelopathy

The function of the spinal cord may also be compromised in individuals infected with HIV. HIV myelopathy is characterized by weakness in the legs and incontinence. Neurological examinations reveal spastic para-paresis and sensory ataxia. Typically, myelopathy manifests in the later stages of HIV disease, and the majority of patients will also exhibit signs of HIV encephalopathy. Pathological assessment of the spinal cord shows vacuolation in the white matter. Since HIV myelopathy is a diagnosis made by exclusion, it is essential to evaluate symptoms indicative of myelopathy through lumbar puncture to eliminate the possibility of CMV polyradiculopathy, as well as conducting an MRI or CT scan to rule out epidural lymphoma.

6. Progressive multifocal leukoencephalopathy (PML)

PML is a viral infection affecting the white matter of the brain, primarily observed in individuals with severely advanced HIV infection. It generally leads to specific neurological deficits, including aphasia, hemiparesis, and cortical blindness. Imaging studies provide strong indications for the diagnosis if they reveal no enhancing white matter lesions accompanied by mass effect. Distinguishing extensive lesions from alterations caused by HIV can be challenging. Numerous patients have shown stabilization or improvement following the initiation of effective ART, and as a result of the widespread use of ART, PML is now infrequently encountered.