The early effects of stavudine compared with tenofovir on adipocyte gene expression, mitochondrial DNA copy number and metabolic parameters in South African HIV-infected patients: a randomized trial.

OBJECTIVES: Stavudine is being phased out because of its mitochondrial toxicity and tenofovir (TDF) is recommended as part of first-line highly active antiretroviral therapy (HAART) in South Africa. A prospective, open-label, randomized controlled trial comparing standard- and low-dose stavudine with TDF was performed to assess early differences in adipocyte mtDNA copy number, gene expression and metabolic parameters in Black South African HIV-infected patients. METHODS: Sixty patients were randomized 1:1:1 to either standard-dose (30-40 mg) or low-dose (20-30 mg) stavudine or TDF (300 mg) each combined with lamivudine and efavirenz. Subcutaneous fat biopsies were obtained at weeks 0 and 4. Adipocyte mtDNA copies/cell and gene expression were measured using quantitative polymerase chain reaction (qPCR). Markers of inflammation and lipid and glucose metabolism were also assessed. RESULTS: A 29% and 32% decrease in the mean mtDNA copies/cell was noted in the standard-dose (P < 0.05) and low-dose stavudine (P < 0.005) arms, respectively, when compared with TDF at 4 weeks. Nuclear respiratory factor-1 (NRF1) and mitochondrial cytochrome B (MTCYB) gene expression levels were affected by stavudine, with a significantly (P < 0.05) greater fall in expression observed with the standard, but not the low dose compared with TDF. No significant differences were observed in markers of inflammation and lipid and glucose metabolism. CONCLUSIONS: These results demonstrate early mitochondrial depletion among Black South African patients receiving low and standard doses of stavudine, with preservation of gene expression levels, except for NRF1 and MTCYB, when compared with patients on TDF.

Lost to follow up: contributing factors and challenges in South African patients on antiretroviral therapy.

BACKGROUND: Patients who do not return for follow-up at clinics providing comprehensive HIV/AIDS care require special attention. This is particularly true where resources are limited and clinic loads are high. Themba Lethu Clinic at Helen Joseph Hospital in Johannesburg is a facility supported by PEPFAR funding through Right to Care (Grant CA-574-A-00-02-00018); more than 800 HIV/AIDS patients are seen there each week. Data on a sample of patients who failed to return for follow-up were analysed to identify the causes and to plan strategies to overcome the problem. METHODS: A group of 182 patients who missed follow-up appointments at the clinic were identified. Their files were examined to identify possible contributing factors. The patients were then contacted telephonically and asked their reasons for non-attendance. RESULTS: Results show that the leading cause of failure to follow up was financial (34% of patients). Patients cited transport costs and having to pay to open a file at each visit as the biggest monetary obstacles to obtaining treatment. Fifty-five per cent of patients lost to follow-up showed an improvement in CD4 count on treatment. Death accounted for 27% of the patients lost to follow-up and the mean ( +/- standard deviation (SD)) duration of treatment in this group was only 8 ( +/- 6) weeks. Of the patients in this group who had been seen at 4 months, 60% had failed to respond to treatment. The mean duration of ARV treatment before being lost to follow-up was 21 ( +/- 28) weeks. The mean CD4+ count was 92 ( +/- 74.5) cells/ microl and the mean number of visits was 3.33 ( +/- 2.17). Seventy-four per cent of the patients were on regimen 1A, and only 1 cited side-effects of medication as a reason for not returning. CONCLUSIONS: This study highlighted financial difficulty as the major obstacle to obtaining treatment. There is evidence in support of providing ARV treatment free of charge to HIVpositive patients who qualify, as occurs in other provinces in South Africa. It is also suggested that providing ARV therapy at more local clinics in the community would make treatment more accessible. Provision of several months' supply of medicines per visit would help to reduce transport costs and minimise patient expenditure. These interventions may reduce the incidence of patients lost to follow-up in this community.

Radiation therapy for non-AIDS associated (classic and endemic African) and epidemic Kaposi's sarcoma.

PURPOSE: A retrospective analysis of patients with non-AIDS and AIDS-related Kaposi's sarcoma, who were treated with radiation therapy. METHODS AND MATERIALS: Between 1978 and 1992, 56 patients with one of the three major types (classical, endemic, epidemic) of Kaposi's sarcoma received radiation therapy as their sole treatment modality. Extent of fields, daily fractionation, and total dose were applied on a clinical basis. These lesions received superficial x-ray therapy, Co-60 teletherapy, or 6-8 MeV electron beams. Field sizes depended on extent of the lesion. Total dose administration ranged from 8-12 Gy in one exposure, or a total of 24-30 Gy fractionated over 2-3 weeks. RESULTS: The majority of patients responded to radiation therapy. Symptomatic relief was achieved in 80-100% of patients irrespective of the type of Kaposi's sarcoma, treatment modality, or schedule. Side effects were tolerable in all but three patients with epidemic type Kaposi's sarcoma, who developed severe mucositis. CONCLUSION: Radiotherapy is the most useful mode of palliative treatment for all forms of Kaposi's sarcoma in southern African patients.

Endemic African Kaposi's sarcoma: clinical and therapeutic implications. 10-year experience in the Johannesburg Hospital (1980-1990).

Endemic African Kaposi's sarcoma is a common neoplastic disorder in the sub-Saharan region of Africa. We present a retrospective analysis of 47 black patients with the endemic African (HIV-negative) variant of Kaposi's sarcoma treated and followed up in the Johannesburg General Hospital between 1980 and 1990. Four patients (8%) presented with simultaneous Kaposi's sarcoma plus malignant lymphoma, indicating a low but significant association with lymphoproliferative disorders. Of 47 patients seen, 29 presented with localized disease and were treated by means of local radiation therapy. Seventeen patients received chemotherapy. The objective response rate was > 80% irrespective of the treatment modality. We conclude that endemic African Kaposi's sarcoma is a chemo- and radiosensitive tumour.

Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption.

The effects of maize-bran phytate and of a polyphenol (tannic acid) on iron absorption from a white-bread meal were tested in 199 subjects. The phytate content was varied by adding different concentrations of phytate-free and ordinary maize bran. Iron absorption decreased progressively when maize bran containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58 mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. The inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent. Studies suggested that greater than or equal to 50 mg ascorbic acid would be required to overcome the inhibitory effects on iron absorption of any meal containing greater than 100 mg tannic acid. Our findings indicate that it may be possible to predict the bioavailability of iron in a diet if due account is taken of the relative content in the diet of the major promoters and inhibitors of iron absorption.

Acute Lymphoblastic Leukaemia in Adults. Prognostic Factors and 10 Year Treatment Results.

One hundred and twenty adult patients with acute lymphoblastic leukaemia were treated over a 10 year period with an intensive treatment protocol including induction with vincristine, prednisolone, adriamycin and L asparaginase, early intensification with 4 cycles of cytosine arabinoside plus VP 16 followed by BCNU and cyclical maintenance therapy consisting of sequential administration of 4 chemotherapy combinations, together with prophylactic in-trathecal methotrexate. 108/120 (90%) achieved initial complete remission (CR). Factors which predicted for CR were absence of bleeding at initial presentation and LDH < 300 Iu. The overall median duration of remission was 12 months with 19% of patients in continuous complete remission for 5 years or more. Among the poor prognostic factors for continuous complete remission were race (black patients) WCC > 30 × 10(9)/1, bleeding at presentation, splenomegaly at presentation, phenotype other than T and age > 35 years. The effect of adverse prognostic features was cumulative but race was the most significant factor overall with no black patients surviving for more than 24 months. There was a significantly higher rate of decreased compliance with maintenance therapy among black patients, which may have been responsible for the adverse influence of race. These results suggest that the role of maintenance chemotherapy is significant in maintaining prolonged complete remission in adult acute lymphoblastic leukaemia.

Von Willebrand's disease in pregnancy. A case report.

A 30-year-old woman with von Willebrand's disease completed her third pregnancy uneventfully. She was infused during labour with fresh frozen plasma and cryoprecipitate. This is in keeping with the good outcome reported in the literature when management is appropriate and surveillance is maintained.

The fate of intravenously administered hepatic ferritin in normal, phenylhydrazine-treated and scorbutic guinea-pigs.

When highly purified hepatic 59Fe-ferritin was injected intravenously into normal guinea-pigs more than half of it was taken up by red cell precursors and the iron was used for haem formation. This was studied in more detail in animals in which a reticulocytosis had been induced either by phenylhydrazine or by repeated venescetions. 55% of the injected ferritin iron was found in reticulocytes at 1 h. Experiments using ferritin doubly labelled with 59Fe and 125I indicated that the whole molecule was taken up, with two-thirds of the radioactivity being associated with the membrane at 1 h and one third being already within the cell. There was a progressive loss of 125I activity over the ensuing hours, while most of the 59Fe was slowly internalized and incorporated into haem between 1 and 24 h. In contrast, 90% of the activity taken up by red cell precursors from 59Fe-transferrin was present as haem at all times. The liver and spleen were the two other major sites of 59Fe-ferritin uptake in phenylhydrazine treated animals. While there was an early uptake of 59Fe into haem in these organs, some redistribution occurred with time, since most of the 59Fe was in a non-haem fraction by 24 h. In a final experiment the distribution and fate of 59Fe-ferritin was studied in scorbutic animals treated with phenylhydrazine. The findings were similar to those in normals similarly treated, which suggests that ferritin iron was being effectively mobilized for haem formation despite the ascorbic acid depletion.