Lopinavir/Ritonavir-Based Antiretroviral Treatment (ART) Versus Efavirenz-Based ART for the Prevention of Malaria Among HIV-Infected Pregnant Women

Autor: Flavia Luwedde, Veronica Ades, Paul Natureeba, Diane V. Havlir, Albert Plenty, Pius Okong, Julia Mwesigwa, Edwin D. Charlebois, Jane Achan, Tamara D. Clark, Deborah Cohan, Bridget Nzarubara, Moses R. Kamya, Grant Dorsey
Rok vydání: 2014
Předmět:
Cyclopropanes
Lopinavir/ritonavir
HIV Infections
Reproductive health and childbirth
Parasitemia
Medical and Health Sciences
Trimethoprim
Lopinavir
chemistry.chemical_compound
Pregnancy
Antiretroviral Therapy
Highly Active
Immunology and Allergy
Pregnancy Complications
Infectious
Pediatric
Sulfamethoxazole Drug Combination
biology
Infectious
efavirenz
lopinavir/ritonavir
Biological Sciences
Treatment Outcome
Infectious Diseases
6.1 Pharmaceuticals
Alkynes
Coinfection
HIV/AIDS
Female
Infection
medicine.drug
Adult
medicine.medical_specialty
Efavirenz
Adolescent
Anti-HIV Agents
Clinical Trials and Supportive Activities
malaria
Antiretroviral Therapy
Microbiology
Antimalarials
Young Adult
Major Articles and Brief Reports
Rare Diseases
Clinical Research
Internal medicine
Trimethoprim
Sulfamethoxazole Drug Combination
parasitic diseases
medicine
Humans
Highly Active
Ritonavir
business.industry
Prevention
Infant
Newborn
Infant
HIV
Evaluation of treatments and therapeutic interventions
Plasmodium falciparum
Newborn
biology.organism_classification
medicine.disease
Benzoxazines
Malaria
Pregnancy Complications
Vector-Borne Diseases
Good Health and Well Being
chemistry
Immunology
business
Zdroj: The Journal of infectious diseases, vol 210, iss 12
ISSN: 1537-6613
0022-1899
Popis: Malaria in pregnancy is associated with adverse maternal and neonatal outcomes, such as spontaneous abortions, stillbirth, intrauterine growth restriction, preterm delivery, low birth weight (LBW), maternal anemia, and neonatal death [1]. Human immunodeficiency virus (HIV)–infected pregnant women have an increased risk of parasitemia, clinical malaria, and placental malaria, compared with HIV-uninfected pregnant women [2]. In addition, coinfection with HIV and placental malaria parasites is associated with an increased risk of low birth weight and preterm delivery, compared with either infection alone [2]. The attributable risk for placental malaria due to HIV infection is more pronounced with higher parity, a phenomenon supported by laboratory studies indicating that HIV impairs parity-specific immunity [3, 4]. Current strategies for the prevention of malaria during pregnancy include the use of insecticide-treated bed nets (ITNs) and intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP). For HIV-infected pregnant women receiving daily trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, the World Health Organization (WHO) recommends avoiding the use of IPTp with SP because of the risk of adverse drug reactions [5]. However, the spread of resistance to the pyrethroid class of insecticides used in ITNs and to the antifolate class of drugs used for ITPp and prophylaxis suggest the need for novel strategies for the prevention of malaria among HIV-infected and uninfected pregnant women [6, 7]. Combination antiretroviral therapy (ART) is now recommended for all HIV-infected pregnant and breast-feeding women per 2013 WHO consolidated guidelines [8]. In addition to benefits in improving women's health and reducing the risk of HIV transmission, the protease inhibitor class of antiretroviral agents may also provide protection against malaria. HIV protease inhibitors demonstrate in vitro activity against Plasmodium falciparum [9–11], and it is thought that this occurs through inhibition of plasmepsins, although the exact mechanism remains unclear [12]. Lopinavir is the most potent of these inhibitors and is active in vitro at levels commonly achieved with ritonavir boosting [10, 11]. In a recent randomized controlled trial of HIV-infected Ugandan children, coformulated lopinavir/ritonavir (LPV/r)–based ART was associated with a 41% reduction in the incidence of malaria, compared with nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based ART, with the lower incidence attributable largely to a significant reduction in the recurrence of malaria after treatment with artemether-lumefantrine (AL) [13]. The efficacy of HIV protease inhibitors for the prevention of malaria and its complications among pregnant women has not been previously evaluated in clinical trials. To test the hypothesis that HIV protease inhibitors are protective against malaria, HIV-infected, ART-naive pregnant women living in an area of Uganda where malaria is highly endemic were randomly assigned to receive LPV/r-based or efavirenz (EFV)–based ART and followed up to 1 year after delivery. Outcomes of interest included measures of placental malaria, adverse birth outcomes, incidence of malaria, and prevalence of asymptomatic parasitemia.
Databáze: OpenAIRE
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