What is the recommended dosage of trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with Human Immunodeficiency Virus (HIV) infection, expressed in milligrams per kilogram per dose and frequency?

From the Guidelines

For Pneumocystis pneumonia (PCP) prophylaxis in HIV-infected patients, the recommended dosage is trimethoprim-sulfamethoxazole (TMP-SMX) 5 mg/kg/dose of the trimethoprim component, given orally once daily, as this dosage has been shown to be effective in preventing PCP while minimizing side effects 1. This prophylaxis is indicated for HIV-infected patients with CD4 counts below 200 cells/μL, as specified in the guidelines for preventing opportunistic infections among HIV-infected persons 1. The following key points should be considered:

• TMP-SMX is the preferred prophylactic agent due to its efficacy, low cost, and additional protection against other opportunistic infections, such as toxoplasmosis and selected common respiratory bacterial infections 1.
• Alternative regimens, including dapsone, atovaquone, and aerosolized pentamidine, may be considered for patients who cannot tolerate TMP-SMX, but these alternatives may be less effective and do not provide the same level of protection against other opportunistic infections 1.
• Renal dose adjustments may be necessary for patients with impaired kidney function, and patients who have experienced adverse events, including fever and rash, may require desensitization or reintroduction of TMP-SMZ at a reduced dose or frequency 1. Some key considerations for the use of TMP-SMX in PCP prophylaxis include:
• The dosage is based on the trimethoprim component to ensure adequate levels for PCP prevention while minimizing side effects 1.
• The guidelines recommend initiating primary prophylaxis for HIV-infected adults and adolescents, including pregnant women and those on HAART, with a CD4+ T lymphocyte count of <200/µL or a history of oropharyngeal candidiasis 1.
• The prophylaxis should be continued until the CD4 count rises above 200 cells/μL for at least 3 consecutive months on antiretroviral therapy 1.

From the FDA Drug Label

For children, the recommended dose is 750 mg/m2/day sulfamethoxazole with 150 mg/m2/day trimethoprim given orally in equally divided doses twice a day, on 3 consecutive days per week.

To convert the recommended dose from milligrams per square meter (mg/m2) to milligrams per kilogram (mg/kg), we need to consider the average body surface area (BSA) of a child. However, the provided information does not directly support the conversion for HIV patients. The FDA drug label does not answer the question.

From the Research

Recommended Dosage of Trimethoprim-Sulfamethoxazole for PCP Prophylaxis

• The recommended dosage of trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with Human Immunodeficiency Virus (HIV) infection is not explicitly stated in terms of milligrams per kilogram per dose and frequency in the provided studies.
• However, according to the study 2, TMP-SMX 960 mg 4 times daily or 3 times daily (approximately TMP 10 mg/kg/day-SMX 50 mg/kg/day) was used to treat PCP in HIV-infected patients.
• Another study 3 mentions that low-dose TMP-SMX (TMP < 12.5 mg/kg/d) was used to treat non-HIV PCP patients, but it does not provide information on the dosage for HIV-infected patients.
• Study 4 discusses the use of lower than recommended dosages of TMP-SMX for PCP prophylaxis in HIV-infected children, but it does not provide a specific dosage in milligrams per kilogram per dose and frequency for adults.

Dosage Comparison

• The study 2 suggests that lower doses of TMP-SMX (approximately TMP 10 mg/kg/day-SMX 50 mg/kg/day) may be equally efficacious and associated with a lower incidence of adverse effects compared to higher doses (approximately TMP 15 mg/kg/day-SMX 75 mg/kg/day).
• Study 3 found that low-dose TMP-SMX (TMP < 12.5 mg/kg/d) was associated with reduced adverse events in non-HIV PCP patients, but it does not provide a direct comparison with HIV-infected patients.

Limitations

• The provided studies do not offer a clear consensus on the recommended dosage of TMP-SMX for PCP prophylaxis in HIV-infected patients, expressed in milligrams per kilogram per dose and frequency.
• More research is needed to determine the optimal dosage of TMP-SMX for PCP prophylaxis in HIV-infected patients, as cited in 2, 4, and 3.