Cotrimoxazole Prophylaxis in HIV-Infected Pregnant Women: Only a First Step

Received 2 August 2006; accepted 2 August 2006; electronically published 19 October 2006. Potential conflicts of interest: none reported. Reprints or correspondence: Dr. D. Heather Watts, Pediatric, Adolescent, and Maternal AIDS Branch, CRMC/NICHD/NIH, Rm. 4B11, 6100 Executive Blvd., MSC 7510, Bethesda, MD 20892 (hw59i@nih.gov). The Journal of Infectious Diseases 2006;194:1478–80 This article is in the public domain, and no copyright is claimed. 0022-1899/2006/19411-0003 In resource-rich countries, during the era before the availability of highly active antiretroviral therapy (HAART), prophylaxis with cotrimoxazole (CTX) was one of the first interventions shown to reduce morbidity and mortality among HIV-infected individuals by reducing the incidence of Pneumocystis jiroveci pneumonia [1]. Prophylaxis with CTX is still recommended for persons with CD4 cell counts!200 cells/ mL, even for those receiving HAART [2]. In resource-limited settings, CTX prophylaxis has also been shown to reduce morbidity and delay death, probably because of the effect that it has on multiple coinfections besides P. jiroveci pneumonia [3, 4]. CTX is inexpensive and is generally well tolerated. However, despite studies demonstrating efficacy in multiple settings, implementation of CTX prophylaxis in resource-limited countries has been slow [5], possibly resulting from perceived differences in the etiology and burden of opportunistic pathogens between resourcelimited and -rich countries, concerns related to the use of CTX prophylaxis in settings with high background malarial and bacterial infections and high rates of bacterial resistance to CTX, and concerns that widespread use of CTX prophylaxis could increase resistance to sulfadoxinepyrimethamine in Plasmodium falciparum. Studies have now demonstrated the efficacy of CTX prophylaxis in multiple settings with a variety of different patterns of bacterial CTX resistance, and, to date, studies have not found that CTX prophylaxis impairs the efficacy of sulfadoxinepyrimethamine in the treatment of malaria [6, 7]. There have been additional barriers to the use of CTX prophylaxis in pregnant women, including concerns about the potential teratogenicity of CTX [8, 9] and the possible effects that CTX may have on folate metabolism that may contribute to low birth weight [10]. In this issue of the Journal of Infectious Diseases, Walter et al. [11] report the results of an opportunistic study of the changes in pregnancy and neonatal outcome after implementation of CTX prophylaxis for pregnant women with CD4 cell counts !200 cells/mL within a larger trial of mother-to-child transmission. The rates of preterm birth, clinical chorioamnionitis, and neonatal mortality were significantly reduced after implementation of CTX prophylaxis, with the benefits being most marked among women with CD4 cell counts !100 cells/mL. No changes in the rates of these outcomes were seen among pregnant women with CD4 cell counts 200 cells/mL over the course of the study. Preterm birth rates remained at 20%–21% in women with CD4 cell counts 200 cells/mL, whereas the rate among women with CD4 cell counts !200 decreased from 31% before to 18% after CTX prophylaxis became available. These results are exciting, because an intervention known to be of benefit for maternal health appears to benefit infant outcomes as well. Earlier concerns regarding the potential toxicity of CTX during pregnancy were not confirmed, although, because of the sample size in Walter et al.’s study, an increase in toxicities such as neonatal jaundice cannot be ruled out. The concern regarding the potential teratogenicity of CTX was addressed by not beginning CTX until 14 weeks of gestation, although the World Health Organization (WHO) recommends the use of CTX throughout pregnancy, because the risk of life-threatening infection among women with low CD4 cell counts or symptomatic HIV infection is felt to outweigh the potential risk of congenital abnormalities [5]. A recent review of the use of CTX during pregnancy did not find evidence to substantiate an increased risk of neonatal jaundice or kernicterus with the use of CTX and found the data on the risk of birth defects to be inconclusive [12]. Conat N aonal Initutes of H ealth L irary on O cber 1, 2013 http://jidrdjournals.org/ D ow nladed from