Preventing Malaria in HIV-Infected Pregnant Women
Preventing Malaria in HIV-Infected Pregnant Women
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.
Dual infection with HIV and malaria adversely affects pregnancy outcome beyond the effects of each single infection. When pregnant women are HIV infected, malaria is more frequent and leads to an increased risk of maternal anemia and low birth weight, which in turn contribute to excess mortality in mothers and infants. Moreover, malaria during pregnancy can increase the maternal HIV viral load, with possible increased transplacental transmission of the virus.
To prevent malaria in HIV-infected pregnant women, the World Health Organization (WHO) currently recommends the use of insecticide-treated bed nets plus preventive drug treatment. To prevent opportunistic infections, immunocompromised women (CD4 cell count <350/mm; WHO HIV clinical stage, >1) receive cotrimoxazole (CTX) prophylaxis that also has antimalarial activity. In less immunocompromised women (CD4 count >350/mm), WHO recommends an intermittent preventive treatment (IPTp) during pregnancy involving at least 3 supervised intakes of an antimalarial drug starting in the second trimester. Of the commonly used IPTp regimens, sulfadoxine-pyrimethamine (SP-IPTp) has been most extensively evaluated both in HIV-negative women and more recently in HIV-infected women. As resistance to sulfa drugs increases rapidly, there is a need to test alternative drugs. A recent trial showed that MQ-IPTp was effective in HIV-negative pregnant women.
However, there is still an important evidence gap in terms of defining optimal malaria prophylaxis for HIV-infected pregnant women, because neither CTX prophylaxis nor alternative drugs to SP in IPTp have ever been evaluated by clinical trials in this specific population. To help fill this gap, we conducted the first randomized controlled trials evaluating CTX for malaria prevention in HIV-infected pregnant women, with MQ-IPTp, alone and in combination, for comparison.
Abstract and Introduction
Abstract
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.
Introduction
Dual infection with HIV and malaria adversely affects pregnancy outcome beyond the effects of each single infection. When pregnant women are HIV infected, malaria is more frequent and leads to an increased risk of maternal anemia and low birth weight, which in turn contribute to excess mortality in mothers and infants. Moreover, malaria during pregnancy can increase the maternal HIV viral load, with possible increased transplacental transmission of the virus.
To prevent malaria in HIV-infected pregnant women, the World Health Organization (WHO) currently recommends the use of insecticide-treated bed nets plus preventive drug treatment. To prevent opportunistic infections, immunocompromised women (CD4 cell count <350/mm; WHO HIV clinical stage, >1) receive cotrimoxazole (CTX) prophylaxis that also has antimalarial activity. In less immunocompromised women (CD4 count >350/mm), WHO recommends an intermittent preventive treatment (IPTp) during pregnancy involving at least 3 supervised intakes of an antimalarial drug starting in the second trimester. Of the commonly used IPTp regimens, sulfadoxine-pyrimethamine (SP-IPTp) has been most extensively evaluated both in HIV-negative women and more recently in HIV-infected women. As resistance to sulfa drugs increases rapidly, there is a need to test alternative drugs. A recent trial showed that MQ-IPTp was effective in HIV-negative pregnant women.
However, there is still an important evidence gap in terms of defining optimal malaria prophylaxis for HIV-infected pregnant women, because neither CTX prophylaxis nor alternative drugs to SP in IPTp have ever been evaluated by clinical trials in this specific population. To help fill this gap, we conducted the first randomized controlled trials evaluating CTX for malaria prevention in HIV-infected pregnant women, with MQ-IPTp, alone and in combination, for comparison.
