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Vitamin D regulates bone metabolism but has also immunoregulatory properties. In HIV-infected patients bone disorders are increasingly observed. Furthermore, low 1,25(OH)(2)D(3) levels have been associated with low CD4(+) counts, immunological hyperactivity, and AIDS progression rates. Few studies have examined the vitamin D status in HIV-infected patients. This study will specifically focus on the effects of antiretroviral agents on vitamin D status. Furthermore, the effect of vitamin D status on CD4 cell recovery after initiation of HAART will be evaluated. Among 252 included patients the prevalence of vitamin D deficiency (<35 nmol/liter from April to September and <25 nmol/liter from October to March) was 29%. Female sex, younger age, dark skin, and NNRTI treatment were significant risk factors in univariate analysis, although in multivariate analyses skin pigmentation remained the only independent risk factor. Median 25(OH)D(3) levels were significantly lower in white NNRTI-treated patients [54.5(27.9-73.8) nmol/liter] compared to white PI-treated patients [77.3 (46.6-100.0) nmol/liter, p = 0.007], while among nonwhites no difference was observed. Both PI- and NNRTI-treated patients had significantly higher blood PTH levels than patients without treatment. Moreover, NNRTI treatment puts patients at risk of elevated PTH levels (>6.5 pmol/liter). Linear regression analysis showed that vitamin D status did not affect CD4 cell recovery after initiation of HAART. In conclusion, 29% of the HIV-1-infected patients had vitamin D deficiency, with skin color as an independent risk factor. NNRTI treatment may add more risk for vitamin D deficiency. Both PI- and NNRTI-treated patients showed higher PTH levels and might therefore be at risk of bone problems. Evaluation of 25(OH)D(3) and PTH levels, especially in NNRTI-treated and dark skinned HIV-1-infected patients, is necessary to detect and treat vitamin D deficiency early.

Herbal medicines are widely used by HIV patients. Several herbal medicines have been shown to interact with antiretroviral drugs, which might lead to drug failure. We have aimed to provide an overview of the modulating effects of Western and African herbal medicines on antiretroviral drug-metabolizing and transporting enzymes, focusing on potential herb-antiretroviral drug interactions. Echinacea, garlic, ginkgo, milk thistle, and St. John's wort have the potential to cause significant interactions. In vitro and in vivo animal studies also indicated other herbs with a potential for interactions; however, most evidence is based on in vitro studies. Further pharmacokinetic studies to unveil potential Western and especially African herb-antiretroviral drug interactions are urgently required, and the clinical significance of these interactions should be assessed.

Plants which are used by traditional healers in Tanzania have been evaluated to obtain preliminary data of their toxicity using the brine shrimps test. The results indicate that 9 out of 44 plant species whose extracts were tested exhibited high toxicity with LC 50 values below 20µg/ml.

The in vitro susceptibilities of 21 Aspergillus isolates were tested against three antifungal agents in RPMI 1640 and yeast nitrogen base at pH 5.0 and 7.0 by a broth microdilution format of the NCCLS method. The MICs of amphotericin B and itraconazole were higher, while those of flucytosine were lower, at pH 5.0 than at pH 7.0. The poor correlation between in vitro results and clinical outcome could be due to a difference in pH between the in vitro susceptibility test and at the site of infection.In vitro susceptibility testing of filamentous fungi has become increasingly important. A good standard in vitro susceptibility test must give reproducible results, predict the resistance of molds, and correlate with clinical outcome (5).In 1998 the National Committee for Clinical Laboratory Standards (NCCLS) proposed a standard method for the determination of the in vitro antifungal susceptibility of conidium-forming filamentous fungi. This document is now approved (3). Although the standardized NCCLS method has been found to give better inter-and intracenter reproducibility, in vitro antifungal susceptibility testing of filamentous fungi is still faced with several problems such as the correlation of in vitro results with clinical outcome.Clinical outcome may be affected by various factors related to the host, the drugs, the fungus, and their interactions (9). These factors are not taken into account in the in vitro tests, and it may be for this reason that the prediction of antifungal efficacy or failure from in vitro susceptibility tests remains difficult. One of the host-related-factors is the pH at the site of infection. In the human body the pH is carefully regulated at 7.4, but it may be lower at the site of infection due to necrosis (7), the production of organic acids by fungi (6), or lysosome activity of granulocytes and macrophages (1).The aim of this study was to investigate the effect of pH on the in vitro activities of three different antifungal agents against 21 Aspergillus isolates in two different media.Twenty-one clinical Aspergillus isolates were tested: five itraconazole (ITZ)-susceptible and five ITZ-resistant Aspergillus fumigatus isolates, five A. flavus isolates, and six A. terreus isolates. Isolates had been frozen in glycerol broth at Ϫ80°C; they were revived by subculturing twice on Sabouraud glucose agar tubes supplemented with 0.5% chloramphenicol and were incubated for 5 to 7 days at 35°C. All isolates were tested in duplicate on different days.Candida parapsilosis ATCC 22019 and C. krusei ATCC 6258 were used for quality control. Amphotericin B (AMB; BristolMyers Squibb, Woerden, The Netherlands), ITZ (Janssen Pharmaceutica B.V., Tilburg, The Netherlands), and flucytosine (5FC; ICN Pharmaceuticals, Zoetermeer, The Netherlands) were obtained as powders. AMB and ITZ were dissolved in dimethyl sulfoxide, and 5FC was dissolved in distilled water. The final concentrations of the antifungal agents at pH 5.0 ranged from 256 to 0.25 g/ml for AMB, from 16 to 0.016 g/ml for ITZ, and from 1,024 to 0...

HIV-infected patients in sub-Saharan countries highly depend on traditional medicines for the treatment of opportunistic oral infections as candidiasis. Previous investigations on antifungal activity of medicinal plant extracts utilized by traditional healers in Tanzania have revealed 12 extracts with potent antifungal activity. Although the plants may be good candidates for new treatment opportunities, they can be toxic or genotoxic and could cause pharmacokinetic interactions when used concomitantly with antiretroviral agents. Therefore, we investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342, Alamar Blue, calcein-AM, glutathione depletion and O 2 -consumption assays and genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP inhibition screening. Pregnane X receptor (PXR) activation was tested using Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing high human PXR activation were tested for enhanced CYP3A4 mRNA levels with quantitative polymerase chain reaction. Genotoxicity was found for Jatropha multifida , Sterculia africana and Spirostachys africana . All plant extracts showed high cytotoxic effects in almost all tests. Potent competition with CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant activation of human PXR, but only Agaura salicifolia , Turraea holstii and S. africana significantly induced CYP3A4 mRNA levels. These results indicate the possibility of potential medicinal plant-antiretroviral interactions.Traditional medicines are commonly used in sub-Saharan countries like Tanzania, with up to 80% of the population depending on traditional medicines for their primary health care [1]. In Tanzania, up to 21% of the people who seeked care from public health care facilities first consult a traditional healer [2]. Especially, HIV-infected persons who often encounter opportunistic infections during their disease course highly depend on this form of health care. According to Medicine du Monde , a French non-governmental organization, in Kagera region, five out of every six HIV-infected patients receive their medical attention from a traditional healer rather than from a hospital or primary health care facility [3]. A survey among 532 HIV patients visiting the HIV clinic of Muhimbili National Hospital, Dar es Salaam, Tanzania, reported use of traditional medicines by 62 patients (11.7%). Focusing on HIV patients with oral lesions, mostly oral Candida infections, a prevalence of traditional medicine use of 40.3% was found [4].Fungal infections, like oral candidiasis, are commonly seen among HIV-infected patients in sub-Saharan Africa. The problems with effective management of these infec...