Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.

Keating, J.; Bjarnason, Ingvar; Somasundaram, Siva G; Macpherson, Andrew J.; Francis, N.; Price, Allison; Sharpstone, D; Smithson, J; Menzies, I. S.; Gazzard, Brian

doi:10.1136/gut.37.5.623

Cited by 132 publications

(106 citation statements)

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“…Keating et al observed that malabsorption and increased intestinal permeability are common in AIDS patients and that malabsorption correlated significantly with the degree of immune suppression and BMI. 8 The study findings demonstrate that adequate nevirapine levels are maintained in blood irrespective of the stage of immune suppression and BMI.…”

Section: Discussionmentioning

confidence: 74%

“…7 Keating et al reported that malabsorption correlates significantly with the degree of immunosuppression. 8 We undertook a study to obtain information on the pharmacokinetics of nevirapine in HIV-infected patients on treatment with FDCs in India, as well as the influence of immunological status, sex, and body mass index (BMI) on the pharmacokinetics of these drugs, as very limited information is available on this aspect. up at regular intervals.…”

mentioning

confidence: 99%

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Steady-State Pharmacokinetics of Nevirapine in HIV-1 Infected Adults in India

Ramachandran

Hemanthkumar

Rajasekaran

et al. 2007

Journal of the International Association of Physicians in AIDS

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Background and Objectives:A variety of demographic factors, sex, and degree of immunosuppression can influence antiretroviral drug concentrations. The authors studied the influence of immune status, sex, and body mass index (BMI) on the steady-state pharmacokinetics of nevirapine delivered as a fixed-dose combination in HIV-1-infected patients in India. Methods: Twenty-six HIV-1-infected adult patients undergoing treatment with nevirapine-based highly active antiretroviral therapy regimens participated in the study. Pharmacokinetic variables were compared between patients divided based on CD4 cell counts, sex, and BMI. Results: Patients with higher BMI had lower peak and trough concentration and exposure of nevirapine than those with lower BMI; none of the differences in the pharmacokinetic variables of nevirapine between the various patient groups was statistically significant. Conclusions: Patients' immune status, sex, or BMI had no impact on the pharmacokinetics of nevirapine. Plasma nevirapine concentrations were maintained within the therapeutic range of the drug in the majority of the patients.Keywords: pharmacokinetics; nevirapine; India; immune status; sex; BMI Access to antiretroviral drugs for HIV-1-infected patients in developing countries is a global public health priority. The World Health Organization currently recommends first-line therapy with 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 non-NRTI (NNRTI)⎯a combination with good efficacy, tolerability, simplicity, and low cost. 1 Generic fixed-dose combinations (FDCs) of such regimens are widely regarded as crucial for scaling up AIDS treatment in developing countries. Two triple-drug combinations consisting of nevirapine and lamivudine with either stavudine or zidovudine as the third agent are available as FDCs in the developing world. A vast majority of HIV-infected patients in India receive nevirapine-based highly active antiretroviral therapy (HAART), the common co-drugs being lamivudine and stavudine. 2 A few studies have reported the effectiveness and safety of generic FDCs for treatment of HIV-1-infected adults. [2][3][4][5] It has been suggested that a variety of demographic factors such as age, body size, and weight can influence antiretroviral drug concentrations. 6 Sex-based differences in the pharmacokinetics of nevirapine have also been observed. 7 Keating et al reported that malabsorption correlates significantly with the degree of immunosuppression. 8 We undertook a study to obtain information on the pharmacokinetics of nevirapine in HIV-infected patients on treatment with FDCs in India, as well as the influence of immunological status, sex, and body mass index (BMI) on the pharmacokinetics of these drugs, as very limited information is available on this aspect. Methods PatientsThe study participants were composed of HIV-infected patients of ethnic Indian origin who were participating in a controlled clinical trial and were being followed

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Section: Discussionmentioning

confidence: 74%

mentioning

confidence: 99%

Steady-State Pharmacokinetics of Nevirapine in HIV-1 Infected Adults in India

Ramachandran

Hemanthkumar

Rajasekaran

et al. 2007

Journal of the International Association of Physicians in AIDS

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“…Serum carotene concentrations are affected by severity of HIV immune disease, gender mix of the population, recent intake and laboratory testing conditions. Besides low dietary intake, low serum carotene concentrations in HIV-infected persons may be because of malabsorption, diarrhea, altered gut barrier function, altered metabolism (Keating et al, 1995) and oxidative stress (Sappey et al, 1994;Allard et al, 1998). The extent of reduction of serum carotene is secondary to its oxidation and consequent depletion by singlet oxygen (Bendich, 1993).…”

Section: Mixed Carotenoids In Hiv Infectionmentioning

confidence: 99%

A community randomized controlled clinical trial of mixed carotenoids and micronutrient supplementation of patients with acquired immunodeficiency syndrome

Austin¹,

Singhal

Voigt³

et al. 2006

Eur J Clin Nutr

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Objective: This clinical trial aims to evaluate if natural mixed carotenoids supplementation can improve the health and survival of acquired immunodeficiency syndrome (AIDS) patients. Design: A placebo-controlled, prospective, randomized, double-blind, multicenter clinical trial. Setting: Community, tertiary care human immunodeficiency virus (HIV) clinics of the Canadian HIV Trials Network (CTN). Participants: Three hundred and thirty-one adults with advanced AIDS on conventional management were recruited during routine clinic visits. Interventions: All participants, including 166 controls, received daily oral specially formulated multivitamins including vitamin A and trace elements; 165 treatment group participants received additional daily oral natural mixed carotenoids, equivalent to 120 000 IU (72 mg) of b-carotene daily. Follow-up was quarterly at routine clinic visits. Results: Mean (s.d.) follow-up was for 13 (6) months. Thirty-six participants died by 18 months. Serum carotene concentration o1.0 mmol/l was present in 16% participants at baseline. Despite variation in carotene content of the treatment medication, serum carotene concentrations increased significantly to twice the baseline levels to 18 months follow-up in participants who received carotenoids treatment compared with controls (Po0.0001). Although not statistically significant, mortality was increased in participants who did not receive carotenoids treatment compared with those who did (HR time to death 1.76, 95% CI 0.89, 3.47, P ¼ 0.11). In multivariate analysis, survival was significantly and independently improved in those with higher baseline serum carotene concentrations (P ¼ 0.04) or higher baseline CD4 T-lymphocyte counts (P ¼ 0.005). Adjusted mortality was also significantly and independently increased in those who did not receive carotenoids treatment compared with those who did (HR time to death 3.15, 95% CI 1.10, 8.98, P ¼ 0.03).

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“…Uma relação entre o grau de imunodeficiência e má absorção foi relatada em adultos com AIDS (42) . Entretanto, em um grupo de crianças infectadas pelo HIV não foi encontrada associação entre baixos níveis de LTCD4+ e má absorção (40) .…”

Section: Padrão De Comportamento Da D-xilose Em Relação àS Variáveisunclassified

“…MILLER et al (52) demonstraram que a má absorção de carboidrato foi relativamente freqüente em crianças HIV positivas assintomáticas, ocorrendo em 40% dos casos. Por outro lado, KEATING et al (42) não evidenciaram má absorção intestinal em pacientes HIV positivos assintomáticos.…”

Section: Introductionunclassified