Cotrimoxazole prophylaxis versus mefloquine intermittent preventive treatment to prevent malaria in HIV-infected pregnant women: two randomized controlled trials.
BACKGROUND
Malaria during pregnancy has serious consequences that are worsened by HIV infection. Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole (CTX) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria, or intermittent preventive treatment (IPTp) with an antimalarial drug. Here, we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp, alone and in combination, in HIV-infected pregnant women.


METHODS
We conducted 2 randomized, open-label, noninferiority trials in Benin. In the CTX-mandatory trial, HIV-infected women with CD4 counts of <350 per cubic millimeter received CTX either alone or with MQ-IPTp (N = 292). In the CTX-not-mandatory trial (CD4 count >350/mm), CTX was compared with MQ-IPTp (N = 140). In both the trials, the primary end point was microscopic placental parasitemia.


RESULTS
At delivery, 1 woman in each CTX-alone treatment group exhibited placental parasitemia, versus no women in the groups receiving MQ. CTX alone demonstrated noninferiority in the CTX-mandatory trial. However, polymerase chain reaction-detected placental parasitemia was markedly reduced in the CTX + MQ group compared with CTX alone (0/105 vs. 5/103, P = 0.03). Because of insufficient recruitment in the CTX-not-mandatory trial, noninferiority could not be conclusively assessed. Dizziness and vomiting of moderate intensity were reported by 34%-37% of women receiving MQ in both the trials, versus 0%-3% in CTX groups (P < 0.0001). No serious adverse events related to these drugs were found.


CONCLUSIONS
CTX alone provided adequate protection against malaria in HIV-infected pregnant women, although MQ-IPTp showed higher efficacy against placental infection. Although more frequently associated with dizziness and vomiting, MQ-IPTp may be an effective alternative given concerns about parasite resistance to CTX.
*UMR 216, Institut de Recherche pour le Développement, Paris, France; †Faculté de Pharmacie, Université Paris Descartes, Paris, France; ‡Centre de Traitement Ambulatoire, Centre National Hospitalier Universitaire Hubert Koutoukou Maga, Cotonou, Benin; §Faculté des Sciences de la Santé, Université d'Abomey-Calavi, Abomey-Calavi, Benin; ‖Inserm U717, Hôpital Saint-Louis, Paris, France; ¶Service de Médecine Interne, Hôpital d'Instructions des Armées, Cotonou, Benin; #Service de gynécologie, Hôpital de la Mère et de l'Enfant Lagune, Cotonou, Benin; **Clinique Louis Pasteur, Porto-Novo, Benin; ††Centre de Traitement Ambulatoire, Hôpital de zone de Suru Léré, Cotonou, Benin; ‡‡Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Antoine, APHP, Paris, France; §§Inserm U707, Université Pierre et Marie Curie, Paris, France.
Lise
L
Denoeud-Ndam
Djimon-Marcel
DM
Zannou
Camille
C
Fourcade
Clément
C
Taron-Brocard
Raphaël
R
Porcher
Felix
F
Atadokpede
Didier G
DG
Komongui
Lucien
L
Dossou-Gbete
Aldric
A
Afangnihoun
Nicaise T
NT
Ndam
Pierre-Marie
PM
Girard
Michel
M
Cot
D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D001541:Benin; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D004244:Dizziness / Q000139:chemically induced / Q000453:epidemiology; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000517:prevention & control*; D015767:Mefloquine / Q000008:administration & dosage* / Q000009:adverse effects; D018512:Parasitemia / Q000517:prevention & control; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control*; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
D000962:Antimalarials; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D015767:Mefloquine