Double-dose lopinavir-ritonavir in combination with rifampicin-based anti-tuberculosis treatment in South Africa

Sunpath, Henry; P, Winternheimer; Cohen, Steven M.; Tennant, I; Chelin, N.; Rt, Gandhi; Murphy, Richard A.

doi:10.5588/ijtld.13.0492

Cited by 13 publications

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“…The antiretroviral treatment has a tremendous impact in the development of acquired immunodeficiency syndrome; it delays relapses and increases the survival and life quality of HIV patients, and greatly reduces the occurrence and severity of opportunistic infections (Santos, 2010 ; Sunpath et al , 2014 ; Lindoso et al , 2016 ). The latter effect has been associated to either a recovery of the immune response or to a direct action of HIV aspartyl peptidase inhibitors (HIV-PIs) on opportunistic pathogens (Santos, 2010 ; Sunpath et al , 2014 ; Lindoso et al , 2016 ). In this sense, HIV-PIs were designed against an aspartyl peptidase from HIV and an orthologous of this enzyme is present at the genome of Leishmania .…”

Section: Introductionmentioning

confidence: 99%

Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism ofLeishmania amazonensispromastigotes

et al. 2018

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The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite.

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Section: Introductionmentioning

confidence: 99%

Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism ofLeishmania amazonensispromastigotes

et al. 2018

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“…A small study of double-dose lopinavir–ritonavir in combination with rifampicin-based antituberculosis treatment in South Africa has shown the favourable outcomes, with 80 % of patients achieving TB treatment success. However, 36 % of patients experienced gastrointestinal toxicity and 12 % had elevated liver enzymes [ 86 ].…”

Section: Introductionmentioning

confidence: 99%

Integrated therapy for HIV and tuberculosis

2016

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Tuberculosis (TB) has been the most common opportunistic infection and cause of mortality among HIV-infected patients, especially in resource-limited countries. Clinical manifestations of TB vary and depend on the degree of immunodeficiency. Sputum microscopy and culture with drug-susceptibility testing are recommended as a standard method for diagnosing active TB. TB-related mortality in HIV-infected patients is high especially during the first few months of treatment. Integrated therapy of both HIV and TB is feasible and efficient to control the diseases and yield better survival. Randomized clinical trials have shown that early initiation of antiretroviral therapy (ART) improves survival of HIV-infected patients with TB. A delay in initiating ART is common among patients referred from TB to HIV separate clinics and this delay may be associated with increased mortality risk. Integration of care for both HIV and TB using a single facility and a single healthcare provider to deliver care for both diseases is a successful model. For TB treatment, HIV-infected patients should receive at least the same regimens and duration of TB treatment as HIV-uninfected patients. Currently, a 2-month initial intensive phase of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by 4 months of continuation phase of isoniazid and rifampin is considered as the standard treatment of drug-susceptible TB. ART should be initiated in all HIV-infected patients with TB, irrespective of CD4 cell count. The optimal timing to initiate ART is within the first 8 weeks of starting antituberculous treatment and within the first 2 weeks for patients who have CD4 cell counts <50 cells/mm3. Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART remains a first-line regimen for HIV-infected patients with TB in resource-limited settings. Although a standard dose of both efavirenz and nevirapine can be used, efavirenz is preferred because of more favorable treatment outcomes. In the settings where raltegravir is accessible, doubling the dose to 800 mg twice daily is recommended. Adverse reactions to either antituberculous or antiretroviral drugs, as well as immune reconstitution inflammatory syndrome, are common in patients receiving integrated therapy. Early recognition and appropriate management of these consequences can reinforce the successful integrated therapy in HIV-infected patients with TB.

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“…Las reacciones adversas a los medicamentos ocurren con más frecuencia entre los pacientes infectados por el VIH con TB que reciben tratamiento simultáneo del VIH y la TB que entre los pacientes no infectados por el VIH." Los perfiles de toxicidad superpuestos comunes incluyen toxicidad hepática, reacciones cutáneas, toxicidad renal y reacciones gastrointestinales" (Sunpath, Winternheimer, & Cohen, 2013). La (tabla 1) muestra los eventos adversos comunes superpuestos de los medicamentos antituberculosos de primera línea y los medicamentos antirretrovirales.…”

Section: Toxicidades Superpuestas De Fármacos Antituberculosos Y Antirretroviralesunclassified

“…Eventos adversos comunes superpuestos de primera líneamedicamentos antituberculosos y medicamentos antirretrovirales. Fuente: (Sunpath, Winternheimer, & Cohen, 2013 Imagen 1. Agrandamiento de los ganglios linfático por TB-SIRI.…”

Section: Toxicidades Superpuestas De Fármacos Antituberculosos Y Antirretroviralesunclassified

Abordaje terapéutico antituberculoso en pacientes con VIH

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La tuberculosis (TB) ha sido la infección oportunista más común y la causa de mortalidad entre los pacientes infectados por el VIH, especialmente en los países con recursos limitados. Las manifestaciones clínicas de la tuberculosis varían y dependen del grado de inmunodeficiencia. La microscopía y el cultivo de esputo con pruebas de sensibilidad a los fármacos se recomiendan como método estándar para diagnosticar la tuberculosis activa. La mortalidad relacionada en pacientes infectados por el VIH es alta, especialmente durante los primeros meses de tratamiento. La terapia integrada tanto del VIH como de la tuberculosis es factible y eficaz para controlar las enfermedades y mejorar la supervivencia. Los ensayos clínicos aleatorizados han demostrado que el inicio temprano de la terapia antirretroviral (TAR) mejora la supervivencia de los pacientes infectados por el VIH con TB. Para el tratamiento de la tuberculosis, los pacientes infectados por el VIH deben recibir al menos los mismos regímenes y duración del tratamiento de la tuberculosis que los pacientes no infectados por el VIH. En tal sentido, la afectación del sistema inmunitario causado por el VIH es un blanco seguro para desarrollar tuberculosis, alterando además, la patogénesis de la tuberculosis lo que genera infecciones pulmonares más agresivas con patrones radiológicos atípicos y presentaciones clínicas diferentes de la enfermedad.

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Double-dose lopinavir-ritonavir in combination with rifampicin-based anti-tuberculosis treatment in South Africa

Abstract: We found the use of double-dose LPV/r during simultaneous standard anti-tuberculosis treatment to be an effective and reasonably well tolerated interim strategy.

Cited by 13 publications

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Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism ofLeishmania amazonensispromastigotes

Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism ofLeishmania amazonensispromastigotes

Integrated therapy for HIV and tuberculosis

Abordaje terapéutico antituberculoso en pacientes con VIH

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