Sensory neuropathy and metabolic risk factors in human immune deficiency virus infected South Africans receiving protease inhibitors

BackgroundProtease inhibitors (PI)s have been associated with distal sensory polyneuropathy (DSP) and metabolic complications in high-income countries. No data exist in Africans where second-line antiretroviral therapy (ART) often include PIs.MethodWe performed a cross-sectional study to assess the DSP frequency and metabolic risk factors in community-based South Africans taking ritonavir-boosted lopinavir as PI. Examination findings categorized subjects as having DSP (≥1 neuropathic sign) or symptomatic DSP [DSP with symptom(s)]. Fasting-state glucose and lipid profiles were assessed. We compared the ritonavir/lopinavir-group to a nested group on first-line ART [dideoxy-nucleoside reverse transcriptase inhibitors (d-drugs)] selected from a dataset collected at the same time and matched for d-drug exposure.ResultsThe ritonavir/lopinavir-group (n=86) consisted predominantly of women (84%) with a median age of 36years (IQR 32–41). The median current CD4+ count was 489cells/μL (IQR 291–665). The median exposure time to ritonavir/lopinavir was 18months (IQR 10–26) and to d-drugs, 24months (IQR 16–38). DSP was present in 78% and symptomatic DSP in 48%; symptoms were most frequently of moderate intensity. Only age independently associated with DSP and symptomatic DSP (p=0.08 and p=0.04, respectively). None of the metabolic syndrome components showed associations with DSP or symptomatic DSP despite a trend towards hypertriglyceridemia overall. The ritonavir/lopinavir-group had less DSP compared to the d-drug only group (p=0.002) but the frequency of symptomatic DSP was similar (p=0.49).ConclusionRitonavir-boosted lopinavir did not add additional risk to developing DSP in this community-based African cohort after a median of 18months on second-line ART.Electronic supplementary materialThe online version of this article (doi:10.1186/s12981-015-0073-8) contains supplementary material, which is available to authorized users

Anti-retroviral therapy increases the prevalence of dyslipidemia in South African HIV-infected patients

Purpose Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. METHODS: We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. RESULTS: The median age of the participants was 34 years (range 19-68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. CONCLUSION: Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon

Tumor-induced osteomalacia: a case report

Background Tumor-induced osteomalacia is a rare, acquired paraneoplastic syndrome, including hypophosphatemia, high serum alkaline phosphatase, reduced active vitamin D, suboptimal bone mineral density, bone pain, fragility fractures, and muscle weakness. Case presentation We report a case of 74–year–old male of mixed ancestry with hypophosphatemia resistant to treatment despite optimal compliance, associated with profound reduction of bone mineral density and multiple nontraumatic fractures, including bilateral rib fractures, lower-thoracic (T11, T12) vertebrae, and two fractures involving the surgical and anatomical neck of the right humerus. We discuss an approach to identifying the underlying cause of hypophosphatemia associated with fragility fractures, and options for management of this rare condition. Conclusion Although rare, tumor-induced osteomalacia can be diagnosed if a logical stepwise approach is implemented. Surgery could be curative if the tumor is properly located and is resectable

Mycosin-1, a subtilisin-like serine protease of Mycobacterium tuberculosis, is cell wall-associated and expressed during infection of macrophages

BACKGROUND: Exported proteases are commonly associated with virulence in bacterial pathogens, yet there is a paucity of information regarding their role in Mycobacterium tuberculosis. There are five genes (mycP1-5) present within the genome of Mycobacterium tuberculosis H37Rv that encode a family of secreted, subtilisin-like serine proteases (the mycosins). The gene mycP1 (encoding mycosin-1) was found to be situated 3700 bp (four ORF's) from the RD1 deletion region in the genome of the attenuated vaccine strain M. bovis BCG (bacille de Calmette et Guérin) and was selected for further analyses due to the absence of expression in this organism. RESULTS: Full-length, 50 kDa mycosin-1 was observed in M. tuberculosis cellular lysates, whereas lower-molecular-weight species were detected in culture filtrates. A similar lower-molecular-weight species was also observed during growth in macrophages. Mycosin-1 was localized to the membrane and cell wall fractions in M. tuberculosis by Western blotting, and to the cell envelope by electron microscopy. Furthermore, M. tuberculosis culture filtrates were shown to contain a proteolytic activity inhibited by mixed serine/cysteine protease inhibitors and activated by Ca(2+), features typical of the subtilisins. CONCLUSIONS: Mycosin-1 is an extracellular protein that is membrane- and cell wall-associated, and is shed into the culture supernatant. The protein is expressed after infection of macrophages and is subjected to proteolytic processing. Although proteolytically active mycosin-1 could not be generated recombinantly, serine protease activity containing features typical of the subtilisins was detected in M. tuberculosis culture filtrates

Factors that influence patient empowerment in inpatient chronic care: early thoughts on a diabetes care intervention in South Africa

Abstract Background The burden of non-communicable diseases is growing rapidly in low- and middle-income countries. Research suggests that health interventions that aim to improve patient self-management and empower patients to care actively for their disease will improve health outcomes over the long-term. There is, however, a gap in the literature about the potential role of the inpatient setting in supporting chronic care. This is particularly important in low-and-middle income countries where hospitals may be a rare prolonged point of contact between patient and health provider. The aim of this small scale, exploratory study was to understand what factors within the inpatient setting may affect patients’ feelings of empowerment in relation to their chronic disease care and provides recommendations for future inpatient-based interventions to support self-management of disease. Methods This study was based in a public, academic hospital in South Africa. Eighteen qualitative, semi-structured interviews were conducted with multiple participants with experience of diabetes care: inpatients and health professionals such as nurses, endocrinologists, and dieticians. Findings were analysed using a broad, exploratory, thematic approach, guided by self-management and chronic care literature. Results Interviews with both patients and providers suggest that patients living in low socio-economic contexts are likely to struggle to access appropriate healthcare information and services, and may often have financial and emotional priorities that take precedence over their chronic illness. Younger people may also be more dependent on their family and community, giving them less ability to take control of their disease care and lifestyle. In addition, hospital care remains bound by an acute care model; and the inpatient setting of focus is characterised by perceived staff shortages and ineffective communication that undermine the implementation of patient empowerment-focused interventions. Conclusions Patient and provider contexts are likely to make supporting patient engagement in long-term chronic care difficult in lower income settings. However, knowledge of these factors can be harnessed to improve chronic care interventions in South Africa and other similar countries

High molecular weight (HMW) : total adiponectin ratio is low in HIV-infected women receiving protease inhibitors

BACKGROUND : At the time of the study, the HIV-treatment policy in South Africa included highly active antiretroviral therapy (HAART) regimens 1 (nucleotide reverse transcriptase inhibitors (NRTIs) only), and 2 (protease inhibitors (PI) and NRTIs). HAART is associated with the lipodystrophy syndrome, insulin resistance and reduced total adiponectin (TA) levels. The high molecular weight (HMW):TA ratio is a superior marker of insulin resistance. The aim of this study was to establish whether HMW:TA ratios are low in patients on PIs and whether they correlate with insulin resistance. METHODS : This was a cross-sectional study undertaken in an antiretroviral clinic at a tertiary hospital. The participants were 66 HIV-infected females: 22 were on regimen 2 (PI group), 22 on regimen 1 (non-PI) and 22 treatment naïve (TN), matched for BMI and age. Patients with a history of diabetes or impaired glucose tolerance were excluded. Serum adiponectin multimers were analysed using the AlpcoTM Adiponectin (Multimeric) enzyme immunoassay. Waist hip ratios (WHR), glucose and insulin levels were assessed, and HOMA-IR and QUICKI calculated. Data were analysed non-parametrically and multivariate analysis was performed. RESULTS : TA and HMW levels were lower in the treatment groups than in the TN group. HMW:TA was lower in the PI than in the non-PI and TN groups, and in the non-PI than in the TN groups. HMW:TA correlated negatively with waist, insulin and HOMA-IR, independently of BMI and duration of therapy. HOMA-IR and QUICKI did not differ among the groups. CONCLUSION : HMW :TA is significantly decreased with HAART (particularly with PIs, but also with non-PIs) and may be a more sensitive marker of insulin resistance in these patients than conventional markers or HMW and total adiponectin individually.National Health Laboratory Service Research Trust Fund, the National Research Foundation, the World Diabetes Foundation and the Department of Health.http://www.biomedcentral.com/bmcclinpathol/hb201

Identification of symptom domains in ulcerative colitis that occur frequently during flares and are responsive to changes in disease activity

<p>Abstract</p> <p>Background</p> <p>Ulcerative colitis disease activity is determined by measuring symptoms and signs. Our aim was to determine which symptom domains are frequent and responsive to change in the evaluation of disease activity, which are those defined by three criteria: 1) they occur frequently during flares; 2) they improve during effective therapy for ulcerative colitis; and 3) they resolve during remission.</p> <p>Methods</p> <p>Twenty-eight symptom domains, 16 from standard indices and 12 novel domains identified by ulcerative colitis patient focus groups, were evaluated. Sixty subjects with ulcerative colitis were surveyed, rating each symptom on the three criteria with a 100 mm Visual Analogue Scale. Frequent and responsive symptoms were defined <it>a priori </it>as those whose median Visual Analogue Scale rating for all 3 criteria was significantly greater than 50.</p> <p>Results</p> <p>Thirteen of the 28 symptom domains were identified as both frequent in ulcerative colitis flares and responsive to changes in disease activity. Seven of these 13 symptom domains were novel symptoms derived from ulcerative colitis patient focus groups including stool mucus, tenesmus, fatigue, rapid postprandial bowel movements, and inability to differentiate liquid or gas from solid stool when rectal urgency occurs. Ten of the 16 symptom domains from standard indices were either infrequent or unresponsive to changes in disease activity.</p> <p>Conclusion</p> <p>Only some of the symptoms of ulcerative colitis that are important to patients are included in standard indices, and several symptoms currently measured are not frequent or responsive to change in ulcerative colitis patients. Development of survey measures of these symptom domains could significantly improve the assessment of disease activity in ulcerative colitis.</p

Factors associated with bone mineral density and bone resorption markers in postmenopausal hiv-infected women on antiretroviral therapy: A prospective cohort study

The study aimed to determine factors associated with changes in bone mineral density (BMD) and bone resorption markers over two years in black postmenopausal women living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART). Women (n = 120) aged > 45 years were recruited from Potchefstroom, South Africa. Total lumbar spine and left femoral neck (LFN) BMD were measured with dual energy X-ray absorptiometry. Fasting serum C-Telopeptide of Type I collagen (CTx), vitamin D and parathyroid hormone were measured. Vitamin D insufficiency levels increased from 23% at baseline to 39% at follow up. In mixed linear models serum CTx showed no change from baseline to end (p = 0.363, effect size = 0.09). Total and LFN BMD increased significantly over two years, but effect sizes were small. No significant change in spine BMD over time was detected (p = 0.19, effect size = 0.02). Age was significantly positively associated with CTx over time, and negatively with total and LFN BMD. Physical activity (PA) was positively associated with LFN BMD (p = 0.008). Despite a decrease in serum vitamin D, BMD and CTx showed small or no changes over 2 years. Future studies should investigate PA interventions to maintain BMD in women living with HIV

Lack of association between stavudine exposure and lipoatrophy, dysglycaemia, hyperlactataemia and hypertriglyceridaemia: a prospective cross sectional study

<p>Abstract</p> <p>Background</p> <p>Stavudine continues to be widely used in resource poor settings despite its toxicity. Our objective was to determine association between plasma stavudine concentrations and lipoatrophy, concentrations of glucose, lactate and triglycerides.</p> <p>Methods</p> <p>Participants were enrolled in a cross-sectional study with lipoatrophy assessment, oral glucose tolerance test, fasting triglycerides, finger prick lactate, and stavudine concentrations. Individual predictions of the area under the concentration curve (AUC) were obtained using a population pharmacokinetic approach. Logistic regression models were fitted to assess the association between stavudine geometric mean ratio > 1 and impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, hypertriglyceridaemia, and lipoatrophy.</p> <p>Results</p> <p>There were 47 study participants with a median age of 34 years and 83% were women. The median body mass index and waist:hip ratio was 24.5 kg/m²and 0.85 respectively. The median duration on stavudine treatment was 14.5 months. The prevalence of lipoatrophy, impaired fasting glucose, impaired glucose tolerance, hyperlactataemia, and hypertriglyceridaemia were 34%, 19%, 4%, 32%, and 23% respectively. Estimated median (interquartile range) stavudine AUC was 2191 (1957 to 2712) ng*h/mL. Twenty two participants had stavudine geometric mean ratio >1. Univariate logistic regression analysis showed no association between stavudine geometric mean ratio >1 and impaired fasting glucose (odds ratio (OR) 2.00, 95% CI 0.44 to 9.19), impaired glucose tolerance (OR 1.14, 95% CI 0.07 to 19.42), hyperlactataemia (OR 2.19, 95%CI 0.63 to 7.66), hypertriglyceridaemia (OR 1.75, 95%CI 0.44 to 7.04), and lipoatrophy (OR 0.83, 95% CI 0.25 to 2.79).</p> <p>Conclusions</p> <p>There was a high prevalence of metabolic complications of stavudine, but these were not associated with plasma stavudine concentrations. Until there is universal access to safer antiretroviral drugs, there is a need for further studies examining the pathogenesis of stavudine-associated toxicities.</p