What are the recommended first‑line treatments for Pneumocystis jirovecii pneumonia and Trichomonas vaginalis infection in an HIV‑positive adult with a CD4 count of 35 cells per microliter?

Treatment of Pneumocystis jirovecii Pneumonia and Trichomonas vaginalis in HIV-Positive Adults

Pneumocystis jirovecii Pneumonia (PJP) Treatment

For an HIV-positive adult with CD4 count of 35 cells/µL presenting with PJP, initiate trimethoprim-sulfamethoxazole (TMP-SMX) at 15-20 mg/kg/day of the trimethoprim component, divided into 3-4 doses every 6 hours for 21 days, with adjunctive corticosteroids if moderate-to-severe disease is present. 1

First-Line Treatment Regimen

• TMP-SMX dosing: Administer 15-20 mg/kg/day of trimethoprim component, divided into 3-4 doses given every 6 hours for 21 days 1
• Route selection: Use intravenous therapy for moderate-to-severe disease; oral therapy may be considered only for mild-to-moderate cases 1
• Treatment duration: Continue for 21 days regardless of clinical improvement 1

Adjunctive Corticosteroid Therapy

Add corticosteroids within 72 hours of diagnosis for any patient with PaO2 <70 mmHg or alveolar-arterial gradient >35 mmHg to reduce mortality, acute respiratory failure, and need for mechanical ventilation. 1

• Adult dosing regimen:
  • Days 1-5: Prednisone 40 mg twice daily 1
  • Days 6-10: Prednisone 40 mg once daily 1
  • Days 11-21: Prednisone 20 mg once daily 1
• Critical timing: Corticosteroids must be initiated within 72 hours of diagnosis to achieve mortality benefit 1

Alternative Regimens for TMP-SMX Intolerance

If TMP-SMX cannot be tolerated, the following alternatives are recommended in order of preference:

For mild-to-moderate disease:

• Atovaquone: 750 mg (1500 mg/day total) orally twice daily with fatty foods for 21 days 1
• Dapsone plus trimethoprim: Dapsone 100 mg daily plus trimethoprim 15 mg/kg/day divided into 3 doses for 21 days (requires G6PD screening before initiation) 1

For moderate-to-severe disease:

• Clindamycin plus primaquine: Clindamycin 600 mg IV every 6 hours for 10 days, then 300-450 mg orally every 6 hours to complete 21 days, plus primaquine 30 mg base orally daily for 21 days (requires G6PD screening) 1
• Intravenous pentamidine: 4 mg/kg once daily with monitoring for hypotension, hypoglycemia, pancreatitis, and nephrotoxicity 1

Important caveat: Pentamidine is associated with significantly greater mortality risk (hazard ratio 2.0-3.3) compared to TMP-SMX and should be reserved for situations where other alternatives cannot be used 2

Managing TMP-SMX Adverse Reactions

• For non-life-threatening reactions (mild rash, fever, mild cytopenias): Continue TMP-SMX if clinically feasible rather than switching agents 1
• Desensitization approach: Up to 70% of patients can tolerate TMP-SMX rechallenge using gradual dose escalation protocols after temporary discontinuation 1
• Rechallenge timing: Attempt rechallenge within 2 weeks of discontinuation for non-life-threatening reactions 1

Critical Monitoring Requirements

• Monitor complete blood count, renal function, electrolytes, and liver enzymes regularly during treatment 1
• Assess clinical response by day 8; consider alternative treatments if no improvement is seen 1
• Watch for common adverse effects including cytopenias, elevated liver enzymes, and renal dysfunction 1

Critical Pitfalls to Avoid

• Never delay corticosteroids beyond 72 hours of diagnosis in moderate-to-severe disease 1
• Never combine pentamidine with TMP-SMX, as this increases toxicity without improved efficacy 1
• Never use dapsone or primaquine without first screening for G6PD deficiency 1

Secondary Prophylaxis After Treatment

• Initiate lifelong secondary prophylaxis following PCP treatment to prevent recurrence, regardless of CD4+ count 1
• Prophylaxis regimen: TMP-SMX one double-strength tablet (800 mg sulfamethoxazole/160 mg trimethoprim) daily, 7 days per week 3
• Alternative prophylaxis: TMP-SMX one double-strength tablet three times weekly 1
• For TMP-SMX intolerance: Dapsone 100 mg daily, or dapsone plus pyrimethamine plus leucovorin, or aerosolized pentamidine 300 mg monthly via Respirgard II nebulizer 3

Discontinuing Secondary Prophylaxis

• Secondary prophylaxis may be discontinued if CD4+ count increases to >200 cells/µL for ≥3 months as a result of HAART 3
• Restart prophylaxis if CD4+ count decreases to <200 cells/µL 3

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Trichomonas vaginalis Treatment

Unfortunately, the provided evidence does not contain specific treatment guidelines for Trichomonas vaginalis infection. The evidence focuses exclusively on Pneumocystis jirovecii pneumonia prophylaxis and treatment.

Based on general medical knowledge, the standard treatment for Trichomonas vaginalis is metronidazole 2 grams orally as a single dose or 500 mg twice daily for 7 days, with treatment of sexual partners. However, this recommendation cannot be cited from the provided evidence and should be verified with current CDC STI treatment guidelines or other authoritative sources specific to trichomoniasis management in HIV-positive patients.