Can cotrimoxazole (trimethoprim/sulfamethoxazole) prophylaxis be given to a 5-month pregnant woman with HIV (human immunodeficiency virus) who is undergoing antiretroviral therapy?

Cotrimoxazole Prophylaxis in Pregnant Women with HIV on Antiretroviral Therapy

Direct Answer

Yes, cotrimoxazole prophylaxis should be administered to a 5-month pregnant woman with HIV undergoing antiretroviral therapy, with TMP-SMZ as the preferred agent. 1

Guideline-Based Recommendations

Primary Prophylaxis Indication

Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) should be administered to pregnant women using the same criteria as other adults and adolescents. 1 This means:

• Initiate cotrimoxazole when CD4+ T-lymphocyte count is less than 200 cells/µL 1
• TMP-SMZ is the recommended prophylactic agent for pregnant women 1
• Dapsone serves as an alternative if TMP-SMZ cannot be tolerated 1

Timing Considerations During Pregnancy

Providers may choose to withhold prophylaxis during the first trimester due to theoretical teratogenicity concerns, but at 5 months gestation (second trimester), this concern no longer applies. 1

• If first-trimester avoidance is desired, aerosolized pentamidine may be considered due to lack of systemic absorption 1
• However, at 5 months (approximately 20 weeks), the patient is well into the second trimester, making TMP-SMZ administration appropriate 1

Additional Benefits Beyond PCP Prevention

The double-strength tablet daily dose of TMP-SMZ recommended for PCP prophylaxis is also effective against toxoplasmic encephalitis in patients with CD4+ counts less than 100/µL. 1 This provides dual protection with a single medication.

Cotrimoxazole prophylaxis in HIV-infected pregnant women with low CD4 counts (less than 200 cells/µL) has been associated with:

• Reduced preterm delivery rates (OR 0.49,95% CI 0.24-0.98) 2
• Significant decrease in neonatal mortality (9% to 0%, P=0.01) 2
• Trend toward increased birth weight 2

Safety Profile in Pregnancy

The overall pooled prevalence of congenital anomalies among women receiving cotrimoxazole during pregnancy is 3.5% (95% CI: 1.8% to 5.1%), which is within the background rate of birth defects. 3

• Neural tube defects showed a crude prevalence of 0.7% (95% CI: 0.5% to 1.0%) with first-trimester exposure 3
• The FDA label notes that some retrospective epidemiologic studies suggest an association with congenital malformations during first-trimester exposure, but these studies had significant limitations 4
• At 5 months gestation, the critical period for neural tube defect formation (first 4 weeks) and major organ development (first trimester) has passed 4

Mortality and Morbidity Benefits

Co-trimoxazole prophylaxis reduces mortality (HR 0.40,95% CI 0.26-0.64) when started at CD4 counts of 350 cells/µL or lower with antiretroviral therapy. 5

In African settings, co-trimoxazole prophylaxis continuation reduces:

• Hospital admissions (HR 0.42,95% CI 0.22-0.80) 5
• Pneumonia (HR 0.73,95% CI 0.61-0.88) 5
• Malaria (HR 0.03,95% CI 0.01-0.10) 5
• Diarrhea (HR 0.61,95% CI 0.48-0.78) 5

Dosing Recommendation

The standard dose is one double-strength tablet (800 mg sulfamethoxazole/160 mg trimethoprim) daily. 1 A 480 mg dose once daily showed non-inferiority to 960 mg once daily without reducing treatment-limiting adverse events 5, but the standard double-strength formulation remains preferred 1.

Integration with Antiretroviral Therapy

Pregnant women should continue both their antiretroviral therapy and cotrimoxazole prophylaxis throughout pregnancy. 1, 6 The combination provides:

• Maternal health protection through ART 6
• Prevention of mother-to-child HIV transmission 7, 6
• Protection against opportunistic infections through cotrimoxazole 1

Critical Pitfalls to Avoid

Do not discontinue cotrimoxazole prophylaxis based solely on viral suppression from ART during pregnancy. While some guidelines discuss discontinuation when CD4+ counts rise above 200 cells/µL for 3-6 months with sustained viral suppression 1, inadequate data exist for pregnant women specifically, and the additional maternal and neonatal benefits support continuation 2, 5.

Do not substitute cotrimoxazole with malaria intermittent preventive treatment (IPTp) in HIV-infected pregnant women. Cotrimoxazole prophylaxis was non-inferior to IPTp for infant mortality, low birthweight, and placental malaria 5, and provides broader protection against opportunistic infections 1.

Monitor for rare but serious adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and blood dyscrasias. 4 Discontinue immediately if skin rash, fever, pharyngitis, or other warning signs develop 4.

Breastfeeding Considerations

Caution should be exercised when administering cotrimoxazole to nursing women, especially with jaundiced, ill, stressed, or premature infants due to potential bilirubin displacement and kernicterus risk. 4 However, levels in breast milk are approximately 2-5% of the recommended infant dose 4.

Postpartum Management

Continue cotrimoxazole prophylaxis postpartum based on the same CD4+ count criteria used for non-pregnant adults. 1 Coordinate care between obstetricians and HIV specialists to ensure continuity 6.