AP is a 77-year-old female with HIV and cachexia. She presents to the hospital complaining of hip pain following a recent fall. She has been off of her medications for an unspecified, prolonged period of time due to social and economic barriers. Various labs are ordered with the results below. 

Labs

CD4+ T-cells 36 cells/mm³ 

HIV-1 RNA, PCR in process

Chest X-ray and CT normal

P. jirovecci PCR negative

T. gondii IgG positive

Blood cultures no growth at 48 hours

Serum cryptococcal antigen: Negative

Allergies: Sulfa (hives and rash)

After reviewing the patient’s lab results and consultation with infectious diseases, it is safe to rule out any active infection. The infectious diseases physician wants to start Biktarvy as soon as possible. Which of the following would you recommend the hospitalist initiate in addition to Biktarvy in order to protect against opportunistic infections? 

A. Azithromycin 1.2g PO once weekly

B. Fluconazole 400 mg PO daily

C. Bactrim DS 800 mg/160 mg PO daily

D. Flucytosine 25 mg/kg PO four times daily

E. Atovaquone 1500mg PO daily

Answer with Rationale

Opportunistic infections are more severe and occur more often in patients with HIV. CD4 cells are T lymphocytes that play a crucial role in immune function. HIV attacks CD4 cells making it harder for these patients to fight off infections. Below are the most common opportunistic infections that occur in patients with HIV.

Pneumocystis jirovecci (PJP) is a fungus found in nature that can cause dyspnea, fever, non-productive cough, and hypoxemia when it is inhaled. Patients are at a higher risk of becoming infected with PJP when their CD4 count is < 200 cells/mm³. 

Toxoplasma gondii is a parasite that can be found in undercooked meat or cat feces. It can cause Toxoplasmic encephalitis (TE) that may manifest as a headache, confusion, and motor weakness. Patients are at the greatest risk of developing TE when their CD4 count is < 50 cells/mm³ but the risk significantly increases once the CD4 count is < 100 cells/mm³.

Mycobacterium avium complex (MAC) is a group of non-tuberculosis mycobacterium and is found in water, soil, and animals. Patients with a CD4 count < 50 cells/mm³ are at risk of developing disseminated disease. This can be characterized by organomegaly, night sweats, fever, abdominal pain, and anemia. 

Cryptococcus neoformans is a fungus found in bird droppings, soil, and decaying wood. It can cause meningoencephalitis due to its ability to enter the CSF, and it can disseminate to any organ. Most cases are seen in patients with a CD4 count < 100 cells/mm³.

It is important to know who is at risk and when to initiate primary prophylaxis against these infections. 

Answer A is incorrect. Prophylaxis against MAC with azithromycin once weekly is appropriate when a patient’s CD4 count is < 50 cells/mm³ AND effective ART is not being initiated immediately. Biktarvy is being initiated as soon as possible in AP, so MAC prophylaxis is not recommended, regardless of her CD4 count.  

Answer B is incorrect. Antifungal prophylaxis is not recommended in patients with HIV unless they have a positive IgM and/or IgG test for Coccidioides. Furthermore, serologic testing for Coccidioides is not recommended unless a patient has lived or traveled to an area where coccidioidomycosis is common, such as the Southwestern United States (e.g. Arizona).

Answer C is incorrect. AP is at risk of developing Toxoplasmosis with a CD4 count < 100 cells/mm³ and being IgG positive. She is also at risk of developing Pneumocystis pneumonia with a CD4 count < 100 cells/mm³, regardless of her HIV RNA viral load. Patients with a CD4 count between 100-200 cells/mm³ are also at risk for development of Pneumocystis pneumonia and would require prophylaxis IF HIV RNA is detected. One double strength tablet of Bactrim daily is sufficient to protect against both of these opportunistic infections. Alternatively, Bactrim one single strength tablet daily or one double strength tablet three times a week would also be appropriate primary prophylaxis regimens. However the answer is incorrect as the patient has a documented sulfa allergy. 

Answer D is incorrect. This would be part of an appropriate treatment regimen with amphotericin B (liposomal) if AP was actively infected with Cryptococcus neoformans. Flucytosine, also known as 5-FC, is never used as monotherapy and often requires serum drug monitoring for management. Furthermore, primary prophylaxis against Cryptococcosis is not indicated in patients with HIV. 

Answer E is correct. Atovaquone is an appropriate monotherapy option for prophylaxis of both Pneumocystis pneumonia and Toxoplasmosis when a patient has a sulfa allergy. Each daily dose of atovaquone should be taken with food. Sulfa allergy is much more common in the HIV population compared to the general population so alternatives are often needed. 

Brand/generic: azithromycin (Zithromax), bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), fluconazole (Diflucan), liposomal amphotericin B (AmBisome), flucytosine (Ancobon), sulfamethoxazole/trimethoprim (Bactrim or Septra), atovaquone (Mepron)

NAPLEX Content Domains Covered:

2.A.2 Indications, usage, and dosing regimens

3.C.1 Signs, symptoms, and findings of medical conditions, etiology of diseases, or pathophysiology

3.C.2 Appropriateness of therapy