Cotrimoxazole prophylaxis in pregnancy

Infants of HIV-positive mothers, particularly women with advanced disease, are at high risk of adverse birth outcomes, including preterm delivery, low birth weight, and infant mortality. The cause of this increased risk is unclear but it may be due to higher risk of maternal infections affecting the infants.

In an oral presentation by Jan Walker of Columbia University, findings from a study in Lusaka, Zambia investigated whether the introduction of cotrimoxazole prophylaxis among HIV positive women with low CD4 counts reduced adverse birth outcomes.

This observational study was conducted within the Zambian Exclusive Breastfeeding Study (ZEBS), which looked at the benefits of early cessation of breastfeeding and enrolled 1435 women between 2001 and 2004. About three quarters of the way through the study in November 2003 – cotrimoxazole prophylaxis was introduced as part of routine HIV care in Zambia for all HIV positive women with CD4 cell counts <200 cells/mm³ (including pregnant women after the first trimester).

The investigators compared the risks of adverse birth outcomes occurring in this cohort before and after the introduction of cotrimoxazole prophylaxis. The women also received malaria prophylaxis, multi vitamins and single dose nevirapine within the ZEBS protocol. Women who received ART before delivery were excluded. Logistic regression was used to adjust for possible changes in other risk factors over this period.

There were 330 women enrolled in the study with CD4 counts <200 cells/mm³, 233 delivered before November 2003 and 97 after this date and who received cotrimoxazole.

Dr Walker reported significant improvements in birth outcomes after the introduction of cotrimoxaxole. Very early preterm birth (</= 34 weeks) declined from 58/188 (31%) to 12/67 (18%), p=0.04. Rate of clinical chorioamnionitis declined from 12/188 (6.4%) to 0/67 (0%), p=0.04. Infant mortality (</= 28 days) declined from 17/188 (9.0%) to 0/67 (0%), p=0.01.

Adjusted for selected medical, obstetric and socio-economic factors before and after the introduction of cotrimoxazole, the only variable that declined significantly was food insecurity from 55/188 (29%) to 10/67 (15%) after introduction of cotrimoxazole, p=0.02. However, Dr Walker noted that this had no effect on outcomes. For birth </=34 weeks: unadjusted OR: 0.49 (95% CI 0.24, 0.98). Adjusted for poverty, maternal education, haemoglobin, low weight, and when enrolled during pregnancy, OR: 0.45 (95% CI 0.22,0.93). There was also a mean increase in birth weight of 100 grams but this did not reach significance.

Additionally, the investigators looked at differences between birth outcomes during the two time periods for women with higher CD4 counts, who were, therefore, not eligible for cotrimoxazole, and found no significant differences.

Dr Walker concluded that cotrimoxazole was most beneficial for women most severely affected by HIV. He speculated that the benefits might be explained by a reduction in preterm birth which could account for up to 80% of infant deaths in this cohort, or that the reduction of maternal infection and in turn infant exposure could account for the improvement in birth outcomes.

He also explained that the study had limitations as it was not randomised nor did it evaluate adverse events associated with cotrimoxazole.

Comment

The ultimate aim of management of HIV in pregnancy is to deliver a healthy uninfected child to a healthy mother. The observation that co-trimoxazole reduces chorioamnionitis with associated reduction in severe pre-term delivery rates and improved infant mortality supports the prescription of co-trimoxazole to pregnant women with advanced HIV despite the theoretical risks. Clearly further studies are required to confirm both this exciting observation.

Walter J, Mwiya M, Scott N et al. Cotrimoxazole prophylaxis and adverse birth outcomes among HIV-infected women in Lusaka, Zambia. 13th Conference on Retroviruses and Opportunistic Infections, 5-8 February 2006, Denver, Colorado. Abstract 126.