HIV/AIDS and Pneumocystis Pneumonia Case File

HIV/AIDS and Pneumocystis Pneumonia Case File

Eugene C. Toy, MD, Gabriel M. Aisenberg, MD

Case 46

A 27-year-old man infected with human immunodeficiency virus (HIV) presents to the emergency department (ED) with a fever of 39.2 °C (102.5 °F). His last CD4 count is unknown. The patient was diagnosed as HIV positive approximately 3 years ago when he presented to his primary care provider with oral thrush. At that time, he was immediately started on highly active antiretroviral therapy (HAART). Approximately 10 months ago, the patient discontinued all treatment due to inability to pay for his medications after losing his job and health insurance. He reports feeling more fatigued recently. For the last 3 to 4 weeks, the patient endorses subjective fevers, a nonproductive cough, and shortness of breath with mild exertion, such as when walking upstairs in his house. The patient noticed unintentional weight loss of approximately 5 pounds over the last 2 months. The patient’s blood pressure (BP) is 134/82 mm Hg, pulse is 110 beats per minute (bpm), and respirations are 28 breaths per minute. Oxygen saturation is 89% on room air but drops to 80% with minimal exertion, and his breathing becomes quite labored. Physical examination shows a cachectic male in mild respiratory distress seated upright in bed. The patient is tachypneic with clear lung fields and white, painless plaques covering his oral mucosa; these plaques are easily scraped off with a tongue depressor. He denies dysphagia. The remaining physical examination is unremarkable. Laboratory testing shows a leukocyte count of 2800 cells/mm3. Serum lactic dehydrogenase (LDH) is 540 U/L (normal 140-280 IU/L). Chest radiograph is shown in Figure 46–1.

▶ What is the most likely diagnosis?

▶ What is your next diagnostic step?

▶ What preventive measure could have significantly reduced the likelihood of developing this disease?

▶ What is the most appropriate next step in management?

Figure 46–1. Chest radiograph: (A) posteroanterior view; (B) lateral view. (Part A, Reproduced with permission, from Braunwald E, Fauci AS, Kasper DL, et al., eds. Harrison’s Principles of Internal Medicine, 15th ed. 2001. Copyright © McGraw Hill LLC. All rights reserved. Part B, Courtesy of Dr. Gabriel Aisenberg.)

ANSWERS TO CASE 46:

HIV/AIDS and Pneumocystis Pneumonia

Summary: A 27-year-old man presents with

• A known HIV infection but unknown CD4 count
• Ten months without antiretroviral therapy or prophylactic medications
• 3 to 4 weeks of fevers, dry cough, weight loss, and worsening dyspnea on exertion
• Febrile temperature of 39 °C, tachycardia, tachypnea
• Oxygen saturation 89% on room air and 80% with minimal exertion
• Painless, white oral plaques that can be scraped
• Chest x-ray showing bilateral, interstitial lung opacities
• Leukocyte count < 3500 cells/mm3, LDH elevated

Most likely diagnosis: Pneumocystis jiroveci pneumonia (PJP); the history, presumed low CD4 count (based on the presence of oral thrush), chest film appearance, and elevated serum LDH make this diagnosis highly suggestive.

Next diagnostic step: Obtain sputum samples for microbiological analysis (specify what you are looking for). Consider a bronchoalveolar lavage if the sputum analysis yields no diagnosis.

Preventive measures: Aside from HAART, prophylactic administration of trimethoprim sulfamethoxazole (TMP-SMX) could have reduced his likelihood of acquiring PJP once his CD4 count dropped below 200 cells/mm3. The most recent guidelines no longer recommend TMP-SMX if the patient takes HAART and has undetectable HIV viral load (not applicable to this patient), regardless of the CD4 count.

Next step in management: The next step is to stabilize the patient. Although hemodynamically stable, he remains tachypneic, hypoxic, and in mild distress. The hypoxemia should be treated with supplemental oxygen or, if needed, endotracheal intubation and mechanical ventilation. An arterial blood gas (ABG) measurement should be obtained to quantify his degree of hypoxemia and initiate proper treatment.

ANALYSIS

Objectives

1. Describe the natural history of HIV infection. (EPA 1, 12)
2. Define the types of opportunistic infections that typically affect HIV-infected patients at various levels of immunocompromise. (EPA 3)
3. Recognize respiratory infections in patients with AIDS. (EPA 1, 10)
4. Identify indications for HAART and for prophylactic medications against opportunistic infections. (EPA 4)

Considerations

This individual with HIV, currently not taking antiviral medications or any antibiotic prophylaxis, presents with subacute dyspnea and cough. His lack of sputum production, hypoxia, and elevated LDH level are suggestive of PJP. The protracted course makes Streptococcus pneumoniae, Mycoplasma, or influenza infection less likely. Mycobacterium tuberculosis can present with atypical radiologic features in severely immunocompromised patients. Other mycobacteria, like Mycobacterium avium-intracellulare complex (MAC); certain fungi, such as Cryptococcus neoformans, Coccidioides immitis, or Aspergillus species; and Nocardia species; and Kaposi sarcoma are only a few examples of a broad differential diagnosis for the patient with AIDS and pulmonary infiltrates. The presence of oral thrush strongly suggests a CD4 count less than 200 cells/mm3; however, oral candidiasis can be present regardless of CD4 count. If laboratory findings reveal a CD4 count lower than 200 cells/mm3, then PJP seems the most likely explanation for his symptoms and chest x-ray findings. Obtaining an ABG measurement will provide additional information about prognosis and guide therapy to determine the utility of corticosteroid administration. Arterial oxygen concentration less than 70 mm Hg on room air or alveolar-arterial gradient (A-a gradient) greater than or equal to 35 mm Hg suggests more severe disease. Treatment with corticosteroids may be helpful when given concurrently with antibiotic therapy, such as TMP-SMX.

APPROACH TO:

HIV/AIDS and Pneumocystis Pneumonia

DEFINITIONS

ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS): An advanced stage of HIV infection in which the CD4 count is lower than 200 cells/mm3 or in which an AIDS-defining illness is diagnosed, regardless of the CD4 count.

PNEUMOCYSTIS JIROVECI (FORMERLY PNEUMOCYSTIS CARINII): A unicellular fungus that causes pneumonia in immunocompromised patients, especially those infected with AIDS.

CLINICAL APPROACH

Pathophysiology

When evaluating a patient with HIV infection and suspected opportunistic infections, determining the level of immunodeficiency via the CD4 count is of clinical significance. Normal CD4 levels in adults range from 600 to 1500 cells/mm3. As levels decline to fewer than 500 cells/mm3, immune function decreases, and patients become increasingly more susceptible to opportunistic infections and/or malignancies.

As many as 40% of patients at the time of initial HIV infection will develop an acute HIV syndrome characterized by sudden onset of a mononucleosis-like illness with fever, headaches, nontender lymphadenopathy, pharyngitis, myalgias, diarrhea, weight loss, and sometimes a macular rash. The most common symptoms are fever, myalgias, and generalized fatigue. The rest of the patients remain asymptomatic and have a clinically latent period of 8 to 10 years, on average, before the clinical manifestations of immunocompromise appear. As CD4 levels decline, the risk of contracting opportunistic infections or reactivation of dormant illnesses increases.

At CD4 levels less than 500 cells/mm3, patients are susceptible to infections, such as recurrent pneumonias, tuberculosis (TB), vaginal candidiasis, and herpes zoster.

At CD4 levels less than 200 cells/mm3, patients are diagnosed with AIDS and are considered significantly immunocompromised. Patients with AIDS can easily contract infections by organisms that rarely cause significant illness in immunocompetent hosts, such as PJP, toxoplasmosis, cryptococcosis, histoplasmosis, and cryptosporidiosis.

At CD4 levels less than 50 cells/mm3, patients are severely immunocompromised and are susceptible to disseminated infection with MAC, cytomegalovirus (CMV) retinitis, colitis, and esophagitis and malignancies such as primary central nervous system (CNS) lymphoma. The Centers for Disease Control and Prevention has published a list of AIDS-defining conditions, which are clinical conditions that define progression from HIV to AIDS (Table 46–1).

Differential Diagnosis. Many other respiratory infections are possible and should be considered in patients with AIDS. Chest radiography helps to narrow down possible diagnoses. Diffuse interstitial lung opacities present in PJP, M. tuberculosis, other mycobacterial infections (such as MAC). Patchy alveolar and nodular lung opacities are also described in the former infections as well as in viral infections, such as CMV. Pleural-based opacities are commonly described in TB and cryptococcal lung disease. Cavitary lesions are seen in TB, PJP, and coccidiomycosis.

In addition to imaging, remember the importance of obtaining a clinical and travel history. Since the most common causes of bacterial pneumonia in AIDS patients are the same organisms that cause pneumonia in immunocompetent hosts, acute onset of fever, and productive cough, along with pulmonary opacities, should suggest community-acquired pneumonia.

A more indolent or chronic history of cough (productive or nonproductive) with weight loss and/or persistent night sweats, especially in high-risk patients (ie, recent exposures, previous incarceration, homelessness or association with shelters, recent emigrant from highly endemic countries, or health care workers), should raise the question of TB. In patients with CD4 count more than 200 cells/mm3, the radiographic appearance of TB is likely to be similar to that of immunocompetent hosts. However, in those with CD4 count lower than 200 cells/mm3, the radiographic appearance is extremely variable; this population often presents with noncavitary pulmonary lesions, lymphadenopathy, and more diffuse presentation of TB (miliary or cutaneous findings). Patients with suspected pulmonary TB should be placed in respiratory isolation until their airborne infectiveness is ruled out. A negative purified protein derivative (tuberculin skin test) or interferon-gamma release assay does not rule out TB in immunocompromised hosts, as they might not be able to mount an immunologic response. Diagnosis and treatment of TB is discussed in Case 44, but it should be noted that TB in AIDS patients primarily spreads hematogenously and produces extrapulmonary manifestations. In HIV patients, Mycobacterium kansasii also causes pulmonary disease and radiographic findings identical to those of M. tuberculosis.

Several other opportunistic infections in AIDS deserve mention. Cerebral toxoplasmosis is the most common central nervous system (CNS) space-occupying lesion in AIDS patients presenting with headache, seizures, or focal neurologic deficits. Contrasted computed tomography (CT) or magnetic resonance imaging (MRI) scans reveal multiple ring-enhancing lesions, often located in the basal ganglia. Presumptive diagnosis often is made based on the radiologic appearance, supported by serologic evidence of infection. Treatment consists of 2 weeks of empiric toxoplasmosis therapy with sulfadiazine and pyrimethamine; the most likely alternative diagnosis is CNS lymphoma. CNS lymphoma usually presents with a single mass lesion but is suspected when presumed lesions of toxoplasmosis do not regress after 2 weeks of specific therapy. If this is the case, historically, the next diagnostic step has been stereotactic brain biopsy. However, recent evidence indicates a next step of examining cerebrospinal fluid (CSF) for Epstein-Barr virus DNA to find malignant lymphocytes that are more likely to be present in immunocompromised patients with CNS lymphoma. Treatment includes starting high-dose methotrexate because of its CNS penetration, glucocorticoids to decrease mass effect, and restarting antiretroviral therapy.

Another CNS complication that requires a high index of suspicion is cryptococcal meningitis. This is a chronic, indolent fungal infection due to C. neoformans, which often presents with vague symptoms, including fever, headaches, fatigue, personality and vision disturbances, and sometimes vomiting or nuchal rigidity; keep in mind that some patients can present with sepsis and in a coma. If the diagnosis is considered, the patient should be screened for evidence of cryptococcal infection by testing for cryptococcal antigen in the serum and via lumbar puncture (LP) for culture.

Imaging (CT or MRI) needs to be performed prior to LP to prevent possible cerebral herniation. The CSF frequently shows mild inflammatory response (ie, low, mostly lymphocytic, white blood cell count; increased CSF protein; and low glucose levels), but the patient often presents with elevated intracranial pressures. Diagnosis can be confirmed by identifying the yeast using, fungal culture or measuring the level of cryptococcal antigen from CSF or serum. Treatment of cryptococcal meningitis requires induction with intravenous amphotericin B plus flucytosine, followed by chronic suppression (consolidation and maintenance) with oral fluconazole. At times, frequent LPs with removal of large volumes of CSF are required to treat the intracranial hypertension, and CSF shunts may be required.

At very low CD4 counts (< 50 cells/mm3), patients with AIDS are also susceptible to CMV infections. This can manifest as viremia with persistent fever, abdominal pain, diarrhea, and other symptoms, including retinitis, which can lead to blindness, esophagitis with severe odynophagia; colitis, and necrotizing adrenalitis, occasionally leading to adrenal insufficiency. Therapy for severe CMV infections includes intravenous ganciclovir, valganciclovir, cidofovir, or foscarnet.

One of the most frequent opportunistic infections occurring in patients with very low CD4 counts (< 50 cells/mm3) is MAC. The most frequent presentations include disseminated infection with persistent constitutional symptoms such as fevers, weight loss, lymphadenopathy, and gastrointestinal symptoms, such as abdominal pain or chronic watery diarrhea. Diagnosis requires a mycobacterial blood culture, which can take up to 10 days for positive results; respiratory or stool cultures have significantly lower sensitivity and specificity. Treatment involves combination therapy, usually beginning with a macrolide (azithromycin or clarithromycin) and ethambutol. The decision to include rifabutin depends on whether the patient is currently doing well on antiretroviral therapy or has a more severe infection. Either way, therapy is continued for a minimum of 12 months.

Clinical Presentation

P. jiroveci pneumonia remains the most common opportunistic infection affecting AIDS patients but often is very difficult to diagnose. The clinical presentation ranges from mild to severe, typically involving fever, dyspnea, nonproductive cough for weeks, significant hypoxemia with respiratory compromise, and worsening fatigue. Some patients experience subjective chills, pleuritic chest pain, and mild weight loss. As many as 5% to 10% of patients are asymptomatic. In addition, the radiographic presentation can be highly variable, ranging from a near-normal chest film to diffuse bilateral interstitial lung opacities. Lung opacities can progress to severe alveolar lung infiltrates, acute respiratory distress syndrome (ARDS) type. Additionally, lung cysts and pleural effusions are occasionally seen. Lung cysts can rupture, causing spontaneous pneumothorax. Suspect PJP in patients presenting with subacute onset of fever, dyspnea, nonproductive cough, and HIV/AIDS without PJP prophylaxis.

Laboratory Findings. Definitive diagnosis can be established by use of Giemsa, direct fluorescence antibody, silver stain, or polymerase chain reaction of sputum or bronchoalveolar lavage. Sputum induction using aerosolized hypertonic saline increases sensitivity. Elevated serum LDH levels may be used as an indirect marker for PJP, although it is nonspecific and may also be elevated in disseminated histoplasmosis or lymphoma. Increasing LDH in the setting of therapy predicts poor prognosis. However, an LDH level less than 220 IU/L is a negative predictor of having PJP. Similarly, in patients with a CD4 count greater than 250 cells/mm3 or those currently taking PJP prophylaxis with TMP-SMX, the diagnosis of PJP should be considered highly unlikely.

Determining the oxygenation levels of patients with PJP via ABG significantly affects prognosis and therapy. Patients with arterial PO2 less than 70 mm Hg or A-a gradient more than 35 mm Hg have significant disease and benefit from the simultaneous use of corticosteroids and antimicrobial therapy.

Treatment

The usual treatment for PJP is TMP-SMX. Alternative therapies for those with sulfa allergies include inhaled pentamidine, clindamycin with primaquine, dapsone, or atovaquone.

HAART includes a combination of at least three drugs, often consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) along with either a nonnucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor, or integrase inhibitor. HAART is very potent and has dramatically revolutionized the treatment of HIV, producing suppression of viral replication and allowing a patient’s CD4 count to recover. Initiation of HAART is usually indicated for all HIV-infected patients at their diagnosis, regardless of being asymptomatic or current immune status.

However, initiation of HAART is not always possible in acutely ill patients because the medications often cause side effects that can be confused with the underlying disease process. Additionally, within 1 to 2 months of starting HAART, worsening of clinical symptoms can occur despite increasing CD4 count, termed immune reconstitution inflammatory syndrome (IRIS), as a result of newly awakened host responses. Therefore, it may be preferable to initiate antiretroviral therapy within 2 weeks of presentation, while consulting an infectious disease expert and establishing reliable follow-up. Guidelines indicate that HAART should be restarted in all AIDS patients within 2 weeks except in cases of cryptococcal meningitis, which requires a delay.

Prevention. Because of the frequency and severity of common opportunistic infections, antimicrobial prophylaxis is routinely given as a patient’s immune status declines. With CD4 counts less than 200 cells/mm3 and a detectable viral load, PJP prophylaxis with either daily or three times a week TMP-SMX is recommended. When CD4 counts fall under 100 cells/mm3 and patients have a positive Toxoplasma serology, toxoplasmosis should be prevented with daily dosing of TMP-SMX. If CD4 levels are less than 50 cells/mm3, a MAC prophylactic regimen with clarithromycin 500 mg twice daily or azithromycin 1200 mg weekly should be started; the current guidelines do not recommend prophylaxis against MAC if the patients take HAART.

CASE CORRELATION

• See also Case 15 (Chronic Obstructive Pulmonary Disease), Case 16 (Chronic Cough/Asthma), Case 18 (Hemoptysis/Lung Cancer), Case 19 (Community-Acquired Pneumonia), Case 44 (Tuberculosis (Pulmonary), Cavitary Lung Lesions), and Case 45 (Syphilis).

COMPREHENSION QUESTIONS

46.1 A 32-year-old woman with a medical history of hypertension, hypothyroidism (treated with levothyroxine), and 5-year history of HIV infection (not adherent to HAART, with most recent CD4 count 87 cells/mm3) is admitted to the hospital with a 2-week history of subjective fever and chills, worsening fatigue, new shortness of breath, and a persistent dry cough. On presentation, her vital signs were the following: 38.3 °C, BP 132/76 mm Hg, heart rate (HR) 105 bpm, respiratory rate (RR) 30 breaths/min, and SpO2 (oxygen saturation as measured by pulse oximetry) 86% on room air. Which of the following diagnostic tests would most likely confirm the diagnosis?

A. Acid-fast smear of the sputum

B. Gram stain of the sputum showing gram-positive diplococci

C. Serum cryptococcal antigen

D. Silver stain or direct fluorescence assay (DFA) of the sputum

46.2 A 67-year-old man with a medical history of hypertension, diabetes mellitus (controlled with insulin), atrial fibrillation (on warfarin), and HIV (restarted on HAART 4 weeks ago) presents to the hospital for 2 days of fever, productive, nonbloody cough, and worsening shortness of breath. His vital signs are the following: temperature 38.3 °C, BP 140/82 mm Hg, HR 109 bpm, RR 26 breaths/min, and SpO2 95% on room air. His current CD4 count is 190 cells/mm3. Which of the following is the most likely organism to cause pneumonia in this patient?

A. Histoplasmosis capsulatum

B. Mycobacterium tuberculosis

C. Pneumocystis jiroveci

D. Streptococcus pneumoniae

46.3 A 44-year-old woman with a medical history of diabetes mellitus (on insulin), chronic kidney disease stage III, and HIV (not adherent to HAART) is noted to have a CD4 count of 180 cells/mm3 during a visit to her primary care provider. Multiple attempts at starting HAART have failed in the past, but she states that she is now ready to start. She is hemodynamically stable with vital signs showing temperature 37 °C, BP 127/73 mm Hg, HR 86 bpm, RR 16 breaths/min, and SpO2 97% on room air. Which of the following is the best therapy to start in this patient?

A. One NRTI, one NNRTI, one protease inhibitor, and TMP-SMX

B. One NRTI, two NNRTI, one protease inhibitor, and TMP-SMX

C. Two NRTI, one integrase inhibitor, and TMP-SMX

D. Two NRTI, one NNRTI, one protease inhibitor, and TMP-SMX

E. Two NRTI, two NNRTI, and TMP-SMX

46.4 A 36-year-old man with a medical history of HIV (not on HAART; CD4 count of 120 cells/mm3) presents with a worsening headache rated 8 on a scale of 0 to 10 and a fever for the last 1 day. His vital signs on presentation are the following: temperature 38 °C, BP 110/58 mm Hg, HR 101 bpm,

RR 16 breaths/min, and SpO2 97% on room air. A CT of his brain is performed and reveals multiple 2-cm solitary lesions. He is started on TMP-SMX with clinical improvement and discharged home with scheduled follow-up in 1 week. Instead, he presents 4 weeks later, brought in by his family after collapsing with a seizure at dinner. The patient is hemodynamically stable. A repeat CT is performed showing the same 2-cm solitary lesions. His wife states that he has been adherent with medications. Which of the following is the next best step?

A. Change therapy to sulfadiazine with pyrimethamine

B. Initiate high-dose methotrexate and glucocorticoids and restart HAART

C. Initiate high-dose methotrexate and glucocorticoids, but delay HAART to avoid IRIS

D. Perform a stereotactic biopsy of the lesion to determine etiology

ANSWERS

46.1 D. The fever, dry cough, and dyspnea are consistent with PJP, which is diagnosed by silver stain or DFA of the sputum. Sometimes, bronchoalveolar lavage is necessary to obtain adequate samples. Sputum Gram stain (answer B) is useful when there is suspicion for a lobar community-acquired pneumonia most commonly caused by Streptococcus pneumoniae, which is more likely to have an acute onset. Acid-fast smear of the sputum (answer A) would help diagnose TB; the absence of clinical clues such as unintentional weight loss, chronic night sweats, and sometimes blood-tinged sputum makes this diagnosis less likely. Cryptococcus (answer C) is more likely to present with CNS involvement (ie, meningitis).

46.2 D. The same organisms that cause community-acquired pneumonia in immunocompetent individuals can cause pneumonia in patients living with HIV. Since Streptococcus pneumoniae is the most common isolate in adult patients with community-acquired pneumonia, it is therefore the most likely etiology. Additionally, HIV patients may be more susceptible to encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae. The fact that symptoms started 2 days ago makes M. tuberculosis (answer B) less likely since it is more of an indolent illness. Disseminated histoplasmosis (answer A) may affect HIV-infected patients as an opportunistic infection and usually manifests as fever, fatigue, chest pain, and respiratory distress; this organism, while found in HIV-infected patients, is not as common as pneumococcal pneumonia. Last, PJP (answer C) tends to present with nonproductive cough and hypoxia, which is not described in this patient.

46.3 C. All HIV-positive patients should be recommended HAART therapy at the time of diagnosis, except in the case of current cryptococcal meningitis. The three-drug therapy consists of two nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) and either one integrase inhibitor, one NNRTI, or one protease inhibitor (thus eliminating answer choices A, B, D, and E). In addition to starting HAART, this patient should receive PJP prophylaxis since her CD4 count is less than 200 cells/mm3. The most common treatment for patients who can tolerate sulfa drugs is TMP-SMX.

46.4 D. This patient should have a biopsy; this is indicated when there is nonresponse to empiric therapy after 14 days. The most common cause of a mass lesion of the brain in an HIV patient is toxoplasmosis, which is treated with TMP-SMX or sulfadiazine and pyrimethamine. However, since this patient failed to show clinical improvement after treatment and still possesses 2-cm brain lesions, primary CNS lymphoma should escalate to the top of the differential diagnosis list. A brain biopsy is diagnostic in that case. Answer A (changing to sulfadiazine with pyrimethamine) would be inappropriate without first ensuring there is no CNS lymphoma. Methotrexate, glucocorticoids, and HAART (answer B) may be a consideration for treating CNS lymphoma, although therapy should not be started without tissue diagnosis. Answer C (methotrexate and steroids without HAART to avoid IRIS) is not indicated. Note that IRIS is a worsening of the neurologic function during the first 60 days of antiretroviral therapy thought to be due to enhanced immune function.

CLINICAL PEARLS

▶ Pneumocystis pneumonia typically has a subacute presentation with fever, a dry cough, and new shortness of breath in HIV patients with a CD4 count lower than 200 cells/mm3 who are not on PJP prophylaxis (TMP-SMX).

▶ Patients with PJP can present with a normal chest x-ray, discrete bilateral interstitial lung opacities, or diffuse severe alveolar lung opacities (ARDS type) and typically have an elevated serum lactic acid dehydrogenase level.

▶ Pulmonary TB should always be considered in AIDS patients with respiratory symptoms and suggestive history; its radiographic presentation may be atypical, and signs and symptoms of dissemination are more common than in immunocompetent patients.

▶ The most frequent isolate in bacterial pneumonia in AIDS patients is S. pneumoniae.

▶ In patients with CD4 counts less than 200 cells/mm3, TMP-SMX prophylaxis is effective in preventing Pneumocystis pneumonia and in preventing toxoplasmosis when the CD4 count is less than 100 cells/mm3.

▶ When the CD4 is less than 50 cells/mm3, clarithromycin or azithromycin are indicated to prevent MAC infection in patients not taking HAART.

▶ HAART is effective in reducing viral replication, increasing CD4 counts, and restoring immunocompetence. With the exception of C. neoformans meningitis, it should not be delayed.

▶ HAART consists of a three-drug treatment: two NRTIs plus one integrase inhibitor, one NNRTI, or one protease inhibitor.

REFERENCES

Brouwer AM, Rajanuwong A, Chierakul W, et al. Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomized trial. Lancet. 2004;363(9423):1764. 

Butt AA, Michaels S, Kissinger P. The association of serum lactate dehydrogenase level with selected opportunistic infections and HIV progression. Int J Infect Dis. 2002;6(3):178. 

Fauci AS, Folkers GK, Lane HC. Human immunodeficiency virus disease: AIDS and related disorders. In: Jameson JL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw Hill; 2018. 

Manoj M, Rajesh KB, Sudesh K, et al. Radiological manifestations of pulmonary tuberculosis—a comparative study between immunocompromised and immunocompetent patients. J Clin Diagn Res. 2017;11(9). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713825/. Accessed July 15, 2019. 

Saag MS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society—USA Panel. JAMA. 2018;320(4):379. 

United States Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2017. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed July 3, 2019.

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