A randomized controlled trial of azithromycin and sulphadoxine–pyrimethamine as prophylaxis against malaria in pregnancy among human immunodeficiency virus–positive women

Abstract

Background Malaria and human immunodeficiency virus (HIV) infections in pregnancy are important and major contributing factors to maternal morbidity and mortality in sub-Saharan Africa. Prevention of malaria in HIV-positive pregnant woman will reduce the burden of malaria–HIV comorbidity. The objective of this study was to compare effects and safety of azithromycin (AZ) with sulphadoxine–pyrimethamine (SP) for intermittent preventive therapy for malaria in HIV-positive pregnant women. Methods We performed a randomized, controlled, open-label pregnancy trial of 140 HIV-positive pregnant patients attending antenatal clinics at the University College Hospital and Adeoyo Maternity Teaching Hospital, Ibadan, Nigeria. Participants were enrolled from a gestational age of 16 weeks and randomized to receive AZ or SP. The primary outcome was peripheral parasitaemia at delivery. Secondary outcomes were drug tolerability, foetal outcome and birthweight. The χ2 test (or Fisher’s exact test, as appropriate) and Student’s t test were used in the per-protocol analysis. The level of statistical significance was p<0.05. Results A total of 123 participants (87.9%) completed the study: 60 participants received AZ and 63 received SP. The incidence of malaria parasitaemia at delivery in the AZ group was 6 (10.0%), compared with 7 (11.1%) in the SP group (relative risk 0.89 [95% confidence interval 0.28 to 2.82], p=0.84). Placental parasitization was demonstrated in 1 (1.6%) participant in the SP group compared with 3 (5.0%) in the AZ group (p=0.36). Conclusions The findings suggest that AZ is comparable to SP in malaria prevention and safety in HIV-positive pregnant women.

Drugs for Intermittent Preventive Treatment of Malaria in Pregnancy: Current Knowledge and Way Forward

“…Safety/tolerability: In that trial, side effects were mild and uncommon, with the exception of nausea, which was significantly higher in the daily AZ arm [38].…”

“…However, when adjusting for potential predictors of placental malaria, the reduction in placental malaria in weekly CQ recipients was statistically significant, suggesting that CQ remains a valuable alternative to IPTp-SP worthy of future research [37]. AZ's efficacy for IPTp is weak [38]. The combination of AZ with CQ yielded poor results, and the combination with piperaquine did not show any advantages in comparison to IPTp-SP [40,89].…”

“…Efficacy: A study performed in Nigeria that compared the use of daily AZ versus monthly IPTp-SP among HIV-infected pregnant women found that both drugs are comparable in terms of efficacy since the prevalence of clinical malaria during pregnancy did not differ significantly among groups [38].…”

The Manifesto of Pharmacoenosis: Merging HIV Pharmacology into Pathocoenosis and Syndemics in Developing Countries

“…From a PD point of view, azithromycin has potential efficacy as a chemoprophylaxis and treatment in several infections, including malaria, trachoma, and both endemic and venereal treponematoses [ 85 , 86 ], as well as an immunomodulant with beneficial effects upon morbidity due to HIV-related chronic lung diseases [ 87 ]. The opportunities and cost-effectiveness of azithromycin administration should be further detailed in settings characterised by significant incidence of HIV, sexually transmitted infections [ 88 , 89 ], malaria [ 85 ], high HIV prevalence among the youngest [ 90 ], both elevated mother-to-child HIV transmission and HIV-positive pregnant women [ 91 , 92 ], increasing household air pollution issues [ 90 , 93 ], and low cART adherence/availability [ 84 ]. In our opinion, the duration and doses of azithromycin in these settings warrant further randomised clinical studies: the drug is potentially able to indirectly reduce HIV transmission (treating sexually transmitted infections and as chemoprophylaxis against malaria) [ 85 , 88 , 89 ], to prevent malaria with promising results in pregnancy [ 91 , 92 ] and to act against a plethora of infectious threats for PLWH in LMIC [ 86 , 90 ] at the cost of a very few adverse events but considerable risk of drug resistance development.…”

A Recent Achievement in the Discovery and Development of Vaccines and Therapeutic Agents in the Race for COVID-19 Protection and Treatment

“…Azithromycin is a macrolide that disrupts RNA-dependent protein synthesis and blocks transpeptidation by binding to 50 s ribosomal subunit and used to treat different bacterial infections such as bacterial conjunctivitis, community-acquired pneumonia, infective endocarditis, mild to moderate respiratory infection, skin and soft tissue infections, bacterial exacerbation of COPD, urethritis, trachomatis, and some others. 73 , 74 Furthermore, azithromycin also effective against different viruses such as Ebola and Zika viruses in the in vitro model. 75 Recently, several clinical trials are ongoing to show the effect of azithromycin against COVID-19.…”