Time filter

Source Type

Wallis C.L.,University of Witwatersrand | Mellors J.W.,University of Pittsburgh | Venter W.D.F.,University of Witwatersrand | Sanne I.,University of Witwatersrand | And 2 more authors.
AIDS Research and Treatment | Year: 2011

Limited data exist on HIV-1 drug resistance patterns in South Africa following second-line protease-inhibitor containing regimen failure. This study examined drug resistance patterns emerging in 75 HIV-1 infected adults experiencing virologic failure on a second-line regimen containing 2 NRTI and lopinavir/ritonavir. Ninety six percent of patients (n=72) were infected with HIV-1 subtype C, two patients were infected with HIV-1 subtype D and one with HIV-1 subtype A1. Thirty nine percent (n=29) of patients had no resistance mutations in protease or reverse transcriptase suggesting that medication non-adherence was a major factor contributing to failure. Major lopinavir resistance mutations were infrequent (5 of 75; 7%), indicating that drug resistance is not the main barrier to future viral suppression. © 2011 Carole L. Wallis et al. Source

Romani B.,Stellenbosch University | Glashoff R.H.,Stellenbosch University | Engelbrecht S.,Stellenbosch University | Engelbrecht S.,National Health Laboratory Services NHLS
Virus Research | Year: 2010

HIV-1 Vpr, an accessory protein with multiple functions, is involved in the induction of apoptosis, cell cycle G2 arrest, and modulation of gene expression. Many functions of this protein have been documented for the wild-type subtype B Vpr, however the functionality of other subtypes has not sufficiently been addressed. In this study, the functionality of Subtype B Vpr, 6 subtype C mutant Vpr proteins and the consensus sequence of subtype C Vpr were compared with each other. All the subtype B and C Vpr proteins localized to the nucleus of human 293T cells. Subtype C Vpr proteins induced cell cycle G2 arrest in a lower proportion of human 293T cells compared to subtype B Vpr. Subtype B and the naturally mutant Vpr proteins induced apoptosis in a similar manner, ranging from 95.33% to 98.64%. However, an artificially designed Vpr protein containing the consensus sequences of subtype C Vpr indicated a reduced ability in induction of apoptosis. The study of mRNA profile of the transfected cells indicated that all Vpr proteins modulated the apoptotic genes triggering the intrinsic pathway of apoptosis. Our results indicate that subtype C Vpr is able to exert the same functions previously reported for subtype B Vpr. Most natural mutations in Vpr not only do not disturb the functions of the protein but also potentiate the protein for an increased functionality. The natural mutations of Vpr may thus not always be regarded as defective mutations. The study suggests the adaptive role of the natural mutations commonly found in subtype C Vpr. © 2010 Elsevier B.V. Source

McCormack V.A.,International Agency for Research on Cancer | Joffe M.,Chris Hani Baragwanath Academic Hospital Breast Clinic | van den Berg E.,National Health Laboratory Services NHLS | Broeze N.,Chris Hani Baragwanath Academic Hospital Breast Clinic | And 6 more authors.
Breast Cancer Research | Year: 2013

Introduction: Estimates of the proportion of estrogen receptor negative (ERN) and triple-negative (TRN) breast cancer from sub-Saharan Africa are variable and include high values. Large studies of receptor status conducted on non-archival tissue are lacking from this region.Methods: We identified 1218 consecutive women (91% black) diagnosed with invasive breast cancer from 2006-2012 at a public hospital in Soweto, South Africa. Immunohistochemistry based ER, progesterone receptor (PR) and human epidermal factor 2 (HER2) receptors were assessed at diagnosis on pre-treatment biopsy specimens. Mutually adjusted associations of receptor status with stage, age, and race were examined using risk ratios (RRs). ER status was compared with age-stratified US Surveillance Epidemiology and End Results program (SEER) data.Results: 35% (95% confidence interval (CI): 32-38) of tumors were ERN, 47% (45-52) PRN, 26% (23-29) HER2P and 21% (18-23) TRN. Later stage tumors were more likely to be ERN and PRN (RRs 1.9 (1.1-2.9) and 2.0 (1.3-3.1) for stage III vs. I) but were not strongly associated with HER2 status. Age was not strongly associated with ER or PR status, but older women were less likely to have HER2P tumors (RR, 0.95 (0.92-0.99) per 5 years). During the study, stage III + IV tumors decreased from 66% to 46%. In black women the percentage of ERN (37% (34-40)) and PRN tumors (48% (45-52)) was higher than in non-black patients (22% (14-31) and 34% (25-44), respectively, P = 0.004 and P = 0.02), which remained after age and stage adjustment. Age-specific ERN proportions in black South African women were similar to those of US black women, especially for women diagnosed over age 50.Conclusion: Although a greater proportion of black than non-black South African women had ER-negative or TRN breast cancer, in all racial groups in this study breast cancer was predominantly ER-positive and was being diagnosed at earlier stages over time. These observations provide initial indications that late-stage aggressive breast cancers may not be an inherent feature of the breast cancer burden across Africa. © 2013 McCormack et al.; licensee BioMed Central Ltd. Source

Wallis C.L.,University of Witwatersrand | Mellors J.W.,University of Pittsburgh | Venter W.D.F.,University of Witwatersrand | Sanne I.,University of Witwatersrand | And 2 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2010

BACKGROUND: The South African national antiretroviral therapy roll-out program is entering its sixth year, with over 570,000 adults accessing treatment. HIV-1 drug resistance is a potential consequence of therapy. This study determined the pattern of HIV-1 drug resistance mutations after failure of first-line treatment regimens in South Africa. METHODS: Two hundred and twenty-six patients virologically failing first-line regimens were studied to determine resistance patterns. RESULTS: The most common reverse transcriptase mutation was M184V/I (72%; n = 163); 11% of patients (n = 25) had only nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations and 17% (n = 38) had no known resistance mutations. The K65R mutation was detected in 4%. The frequency of thymidine analog mutations was significantly higher with azidothymidine-containing (31 of 57) than stavudine-containing regimens (39 of 169; P < 0.001). The Y181C mutation was more frequent with failure of nevirapine (NVP)-containing (26%) than efavirenz (EFV)-containing therapy (3%; P < 0.001). The V106M mutation was more frequent with EFV (30%) than NVP (4%; P = 0.012). CONCLUSIONS: HIV-1 drug resistance patterns varied broadly after failure of first-line therapy, ranging from no known resistance mutations (17%) to multinucleoside reverse transcriptase inhibitor and NNRTI resistance (23%). NNRTI mutation profiles differed for patients on EFV-compared with NVP-containing regimens. Overall, these findings suggest that HIV-1 drug resistance testing would be useful in identifying most appropriate second-line regimens. Copyright © 2010 by Lippincott Williams & Wilkins. Source

Cordier W.,University of Pretoria | Cromarty A.D.,University of Pretoria | Botha E.,National Health Laboratory Services NHLS | Steenkamp V.,University of Pretoria
Human and Experimental Toxicology | Year: 2012

The use of herbal preparations for staunching blood flow and reducing the risk of vascular thrombosis is common worldwide. In this study, aqueous and methanolic extracts of plants used to treat blood-associated complaints were investigated to determine their effects on red blood cell haemolysis and coagulation. The extent of haemolysis was determined spectrophotometrically. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) as indicators of coagulation rate were determined using a coagulatometer. All of the plant extracts tested had a significant effect on coagulation time, prolonging the aPTT. Cassia petersiana had the greatest prolonging effect on PT compared to the control, phosphate buffered saline (PBS). As all of the herbal extracts tested had a delaying effect on coagulation, patients using herbal/plant therapies should be cautioned to stop their medication before surgery. © SAGE Publications 2012. Source

Discover hidden collaborations