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/mm3), 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.
Correspondence to: Lise Denoeud-Ndam, MD, PhD, Clinical Research Department, Epicentre, 8 rue Saint-Sabin, 75012 Paris, France (e-mail: firstname.lastname@example.org).
Supported by Sidaction Grant AI19-3-01528.
The authors have no conflicts of interest to disclose.
Intermediate results presented at the Seventh European Congress of Tropical Medicine and International Health (ECTMIH), October 2011, Barcelona, Spain.
Clinical trials registration number: NCT00970879, www.clinicaltrials.gov.
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Received June 12, 2013
Accepted November 02, 2013