Track topics on Twitter Track topics that are important to you
HIV and malaria are major causes of morbidity and mortality in Sub-Saharan Africa and children bear the greatest brunt of both diseases. No single existing intervention is likely to control malaria in Africa. Rather, improvements in malaria prevention are likely to come from strategies that employ multiple proven interventions targeting different populations. HIV-infected children represent one of the most vulnerable subpopulations in these countries. It is possible that the use of protease inhibitor (PI) - based antiretroviral therapy (ART) in HIV-infected children living in areas of high malaria transmission could prevent malaria in this vulnerable population. An effective remedy that offers the possibility to further reduce malaria risk, such as PIs, is highly desirable. This study will determine whether a PI based ART regimen will reduce malaria among children living in a malaria endemic area of Uganda and receiving insecticide-treated bed nets (ITN) and TS. This study will compare two different ART regimens. Children enrolled in the study will start or continue to receive either standard Ugandan first line treatment ART regimen (NNRTI+2 NRTIs) or an ART regimen containing the HIV protease inhibitor (lopinavir/ritonavir +2 NRTIs) and followed for a period of 24 months.
This is an open label, single site, randomized clinical trial comparing PI-based ART to NNRTI-based ART for the prevention of malaria in HIV-infected children. The two ART drug regimens that will be used include: Treatment arm 1. LPV/r + 2 NRTIs and Treatment arm 2. NVP or EFV + 2 NRTIs. The study is designed to test the hypothesis that children receiving a PI-based ART regimen will have lower the incidence of malaria compared to children receiving an NNRTI- based ART regimen. The primary study endpoint of the study is malaria incidence.
The study site will be the Tororo District Hospital campus situated in Eastern Uganda, an area of high malaria transmission. Using convenience sampling, 300 HIV-infected children identified from the Tororo community aged 2 months to 5 years either eligible for ART-initiation or already receiving a first line ART regimen with HIV RNA<400 copies/ml will be evaluated for enrollment.
Eligible children will be randomized at enrollment to receive either a PI- based or an NNRTI-based ART regimen. At enrollment, all study participants will receive a long lasting ITN as part of a basic care package including a safe water vessel and multivitamins and given TS chemoprophylaxis, as per current standard of care for HIV-infected children in Uganda. On the day of ART initiation, patients will be counseled about the importance of adherence to ART and possible ART related toxicities. After 2 weeks, patients will be seen to assess adherence and toxicity to study medications by interview and clinical examination. Apart from this visit at week 2, patients will be seen at 4 week intervals timed from ART-initiation. Assessment of adherence will also be done for TS prophylaxis, ITN use and ART. Assessment of adherence to ART will be done by self report of missed doses and pill counts.
Participants will receive all routine and acute medical care at a designated study clinic open 7 days a week from 8 a.m. to 5 p.m. Parents/guardians will be asked to bring their child to the study clinic for all medical care. If after hours, they will be instructed to bring them to Tororo District Hospital premises (where the study clinic is located) and request that the study physician on-call be contacted. They will be followed for at least 24 months and up to 3 years. They will be seen monthly for routine assessments with laboratory evaluations done at every 3 months. At these visits, the study protocol will be reinforced with discussion regarding the need to come to the study clinic promptly upon the onset of any illness and to avoid use of outside medications. Study participants will also be followed closely for adverse events potentially due to study drugs and for malaria and HIV treatment outcomes. During the follow-up period, all patients presenting to the clinic with a new episode of fever will undergo standard evaluation (history, physical examination) and Giemsa-stained blood smear for the diagnosis of malaria.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
LPV/r + 2 NRTIs, NVP or EFV + 2 NRTIs
IDRC - Tororo Research Clinic
University of California, San Francisco
Published on BioPortfolio: 2014-08-27T03:19:18-0400
A study comparing Indinavir plus Ritonavir plus 2 NRTIs vs. Nelfinavir 1250 plus two nucleoside reverse transcriptase inhibitors (NRTIs) in the treatment of HIV positive patients who have ...
A switch to a regimen consisting of ATV/RTV 300/100 mg QD + 3TC 300 mg QD in HIV-1 infected subjects in their first antiretroviral regimen and who are virologically suppressed on a regimen...
The substitution of raltegravir for the NRTIs will result in some reversal of the long term adverse effect of lipodystrophy (specifically peripheral lipoatrophy) that is associated with th...
This study will compare an anti-HIV drug combination of protease inhibitor plus a nonnucleoside reverse transcriptase inhibitor (NNRTI) to one that includes three nucleoside reverse transc...
Study of Lopinavir/Ritonavir Tablets Versus Soft Gel Capsules and Once Daily Versus Twice Daily Administration, When Coadministered With Nucleoside Reverse Transcriptase Inhibitors in Antiretroviral Naive Human Immunodeficiency Virus Type 1 Infected Subje
The purpose of this study was to compare the safety and tolerability of the to-be-marketed lopinavir/ritonavir (LPV/r) tablet formulation with the marketed soft gel capsule (SGC) formulati...
Use of some HIV-1 nucleoside reverse transcriptase inhibitors (NRTI) is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitoch...
Nucleoside reverse transcriptase (RT) inhibitors (NRTIs) are the backbone of current antiretroviral treatments. However, emergence of viral resistance against NRTIs is a major threat to their therapeu...
After first-line antiretroviral therapy (ART) failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second-line is uncertain due to the high potency of protease inh...
The increasing prevalence of mutations in HIV-1 reverse transcriptase (RT) that confer resistance to existing NRTIs and NNRTIs underscores the need to develop RT inhibitors with novel mode-of-inhibiti...
The effects of abacavir were evaluated in a validated model of arterial thrombosis. The role of ATP-P2X7-receptors and the actions of two vascular-damaging agents (diclofenac or rofecoxib) and other N...
Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.
Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents.
A protozoan parasite that causes vivax malaria (MALARIA, VIVAX). This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions.
Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.
A protozoan parasite that occurs naturally in the macaque. It is similar to PLASMODIUM VIVAX and produces a type of malaria similar to vivax malaria (MALARIA, VIVAX). This species has been found to give rise to both natural and experimental human infections.
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...