Efficacy of Antifolates Against Malaria in HIV-infected Pregnant Women and the Emergence of Induced Resistance in Plasmodium Falciparum

• Status: Completed
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

Given the resistance emergence of malaria in pregnant women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPT-SP) and the burden of this infection among pregnant women infected by HIV it is urgent to seek a more effective alternative treatment to optimize the prevention of malaria. Cotrimoxazole (CTM), actually administered daily as a prophylactic mean to opportunistic infections for HIV infected patients, showed encouraging results in preventing malaria in pregnant women. However, these results must be confirmed by randomized trials, particularly in pregnant women.

The main objective of this clinical trial is to compare the efficacy of cotrimoxazole (CTM), administered once daily with IPT-SP (3 curative doses spaced one month) on placental parasitaemia in pregnant women infected with HIV and cluster of differentiation 4 (CD4) > 350 cells/mm3.

The main hypothesis is based on the premise that cotrimoxazole is more effective than IPT-SP for placental parasitaemia. This might be due to the higher plasma concentration of cotrimoxazole attained with daily doses. If this hypothesis is proven, cotrimoxazole could be recommended as prophylaxis for HIV-positive pregnant women, whatever their CD4+ cell count. In this study, the investigators will also test the hypothesis that the strains of Plasmodium falciparum isolated from HIV-positive pregnant women express more dhfr and dhps resistance markers.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut Pasteur
• Collaborator: Institut Pasteur de Bangui
• Treatments: Fanasil, pyrimethamine drug combination; Folic Acid Antagonists; Pyrimethamine; Sulfadoxine; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination

Criteria

Inclusion Criteria:

• age ≥ 18 years

• HIV positivity

• gestational age between 16 and 28 weeks

• CD4+ count > 350 cells/mm3 and no sign of WHO stage 2, 3 or 4;

• agreement to attend all the antenatal consultations for the study

• willingness to adhere to all requirements of the study (including HIV-1 voluntary counseling and testing)

• signed informed consent

Exclusion Criteria:

• psychological instability that could interfere with compliance;

• hypersensitivity to sulfamides or dermatological disease(eczema, pemphigoid exanthema) that would increase the risk for severe reactions to the drugs being tested

• severe anaemia (Hb<7 g/dl)and any other severe disease

• known hepatic cardiac or renal disease