Systematic Review of the Safety of Trimethoprim-Sulfamethoxazole for Prophylaxis in HIV-Infected Pregnant Women: Implications for Resource-Limited Settings
Fatu Forna 1, Michelle McConnell 1, Florence N. Kitabire 1, Jaco Homsy 1, John T. Brooks 1, Jonathan Mermin 1
1 NULL
*Correspondence: Fatu Forna, Email not available
Abstract
Daily prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) significantly decreases morbidityand mortality among people living with HIV. Some clinicians are reluctant to use TMP-SMZ in pregnantand breastfeeding HIV-infected women because of concerns about the possible teratogenicity whenused in the first trimester and about its potential to induce hyperbilirubinemia near term and duringearly breastfeeding.We systematically reviewed evidence regarding the toxicity of TMP-SMZ prophylaxis in pregnant andbreastfeeding women to help guide practice in resource-limited settings. We identified relevant literatureby searching PubMed and MEDLINE via OVID, Embase, and Science Citation Index for dataon hyperbilirubinemia, kernicterus, and teratogenicity associated with administration of sulfonamidesand TMP-SMZ through July 2005. We also reviewed the reference lists of identified articles.Most studies demonstrated that TMP-SMZ was not associated with hyperbilirubinemia when administeredto mothers during pregnancy and breastfeeding. No cases of kernicterus were reported inneonates after maternal ingestion of sulfonamides. There is mixed evidence linking ingestion of TMPSMZand other sulfonamides in early pregnancy to elevated risks of oral clefts, neural tube defects,and cardiovascular and urinary tract abnormalities, although some sources found that supplementationwith folic acid might ameliorate this potential risk. Existing guidelines recommend that HIV-infectedpregnant women receive prophylaxis, but they differ with regards to stage of disease at whichto initiate treatment, need for CD4+ T-lymphocyte testing, and prophylaxis during the first trimester.Existing data indicate that the risk of serious injury to neonates from maternal use of daily TMP-SMZprophylaxis during pregnancy and breastfeeding is small. Given the substantial benefits of TMP-SMZprophylaxis for HIV-infected women living in resource-limited settings, this review indicates that it issafe to abide by the WHO guidelines recommending daily TMP-SMZ prophylaxis for HIV-infectedpregnant women.
