Azithromycin Addition to TMP-SMX Fails to Reduce Malaria and STI Risk in Pregnant Women with HIV: Study

Malaria and sexually transmitted infections pose significant health risks to pregnant women, particularly those living with HIV. The standard prophylactic regimen involves daily TMP-SMX, which has shown efficacy in reducing certain infections. This study hypothesized that the addition of azithromycin, known for its broad-spectrum antibiotic properties, would further reduce the rates of malaria and bacterial STIs at delivery.

This randomized, controlled trial enrolled 308 pregnant women with HIV, all under 28 weeks of gestation. Participants were randomized into two groups: 155 women received TMP-SMX with monthly azithromycin (1 gram daily for three days), and 153 women received TMP-SMX with a placebo. The primary outcomes were the presence of peripheral malaria infection (detected by microscopy or PCR) and a composite measure of bacterial genital STIs (including C. trachomatis, N. gonorrhoeae, and syphilis) at delivery. Statistical analysis involved estimating relative risks (RR) and 95% confidence intervals (CI) using 2 × 2 tables, with significance set at p < 0.05.

Results:

• A total of 308 women were enrolled, with a loss to follow-up rate of 3.2%. The baseline characteristics of the groups were similar.

• At delivery, 16.3% of women in the TMP-SMX-AZ group had malaria, compared to 13.2% in the TMP-SMX group (RR 1.24, 95% CI 0.71-2.16, p=0.12).

• The incidence of bacterial STIs was 4.2% in the TMP-SMX-AZ group versus 5.8% in the TMP-SMX group (RR 0.72, 95% CI 0.26-2.03, p=0.28).

• There were no significant differences in adverse birth outcomes. Preterm delivery occurred in 6.7% of the TMP-SMX-AZ group and 10.7% of the TMP-SMX group (p=0.3).

• Low birth weight was observed in 3.4% of the TMP-SMX-AZ group and 5.4% of the TMP-SMX group (p=0.6)

The study's findings indicate that the addition of azithromycin to the standard TMP-SMX regimen does not provide additional protection against malaria or bacterial STIs at delivery for pregnant women with HIV. These results align with previous research that has shown mixed outcomes for azithromycin in similar contexts.

The trial concluded that adding monthly azithromycin to daily TMP-SMX prophylaxis does not significantly reduce the risk of malaria or bacterial STIs at delivery in pregnant women with HIV in Cameroon. Future research should explore alternative strategies to enhance infection prevention in this high-risk population.

Reference:

Dionne, J. A., Anchang-Kimbi, J., Hao, J., Long, D., Apinjoh, T., Tih, P., Mbah, R., Ngah, E. N., Juliano, J. J., Kahn, M., Bruxvoort, K., Van Der Pol, B., Tita, A. T. N., Marrazzo, J., & Achidi, E. (2024). Trimethoprim-sulfamethoxazole plus azithromycin to prevent malaria and sexually transmitted infections in pregnant women with HIV (PREMISE): A randomized, double-masked, placebo-controlled, phase IIB clinical trial. Open Forum Infectious Diseases. https://doi.org/10.1093/ofid/ofae274