This patient should begin azithromycin. Because his CD4 cell count is less than 50/µL, he is at significant risk for disseminated Mycobacterium avium complex infection and should begin prophylaxis immediately with azithromycin. He has HIV infection and meets the definition for AIDS based on a CD4 cell count less than 200/µL. Although he has not yet had an opportunistic infection, he should also receive prophylaxis against Pneumocystis jirovecii, for which daily trimethoprim-sulfamethoxazole is the drug of choice.

Although this patient is at risk for candidal infections, such as oroesophageal disease, or infection by other fungi, including Cryptococcus neoformans, primary antifungal prophylaxis is not recommended in HIV infection. Therefore, fluconazole is not indicated in this patient.

The risk for tuberculosis (TB) infection increases in patients following HIV seroconversion and increases as loss of CD4 cells and immunosuppression progress. Therefore, all patients with HIV infection should be screened for latent TB, and close follow-up for primary TB infection should be maintained. However, this patient has no evidence of latent or active TB infection. The interferon-γ release assay result is indeterminate because of his very low CD4 count and consequent inability to react to the positive control used in the testing. He has no clinical symptoms or signs of TB and has not had any exposure. Therefore, treatment with isoniazid and vitamin B₆ is not indicated.

Pyrimethamine is an agent with activity against Toxoplasma gondii, which this patient is at risk for based on his positive serologic results and CD4 cell count less than 100/µL. Leucovorin is given concomitantly to lessen the risk for cytopenias, which are a common adverse effect associated with pyrimethamine therapy. However, the trimethoprim-sulfamethoxazole already being used for Pneumocystis prophylaxis will also protect against toxoplasmosis, so additional medication is unnecessary.

Although the patient is at risk for reactivation disease due to cytomegalovirus, primary prophylaxis is not recommended because of the hematologic toxicity of valganciclovir.