Browsing by Author "Zembe, Lycias"

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    Intra- and inter-clade cross-reactivity by HIV-1 gag specific T-cells reveals exclusive and commonly targeted regions : implications for current vaccine trials
    (Public Library of Science, 2011-10-12) Zembe, Lycias; Burgers, Wendy A.; Jaspan, Heather B.; Bekker, Linda-Gail; Bredell, Helba; Stevens, Gwynneth; Gilmour, Jill; Cox, Josephine H.; Fast, Patricia; Hayes, Peter; Vardas, Eftyhia; Williamson, Carolyn; Gray, Clive M.
    ENGLISH ABSTRACT: The genetic diversity of HIV-1 across the globe is a major challenge for developing an HIV vaccine. To facilitate immunogen design, it is important to characterize clusters of commonly targeted T-cell epitopes across different HIV clades. To address this, we examined 39 HIV-1 clade C infected individuals for IFN-c Gag-specific T-cell responses using five sets of overlapping peptides, two sets matching clade C vaccine candidates derived from strains from South Africa and China, and three peptide sets corresponding to consensus clades A, B, and D sequences. The magnitude and breadth of T-cell responses against the two clade C peptide sets did not differ, however clade C peptides were preferentially recognized compared to the other peptide sets. A total of 84 peptides were recognized, of which 19 were exclusively from clade C, 8 exclusively from clade B, one peptide each from A and D and 17 were commonly recognized by clade A, B, C and D. The entropy of the exclusively recognized peptides was significantly higher than that of commonly recognized peptides (p = 0.0128) and the median peptide processing scores were significantly higher for the peptide variants recognized versus those not recognized (p = 0.0001). Consistent with these results, the predicted Major Histocompatibility Complex Class I IC50 values were significantly lower for the recognized peptide variants compared to those not recognized in the ELISPOT assay (p,0.0001), suggesting that peptide variation between clades, resulting in lack of cross-clade recognition, has been shaped by host immune selection pressure. Overall, our study shows that clade C infected individuals recognize clade C peptides with greater frequency and higher magnitude than other clades, and that a selection of highly conserved epitope regions within Gag are commonly recognized and give rise to cross-clade reactivities.
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    Strengthening HIV surveillance in the antiretroviral therapy era : rationale and design of a longitudinal study to monitor HIV prevalence and incidence in the uMgungundlovu District, KwaZulu-Natal, South Africa
    (BioMed Central, 2015) Kharsany, Ayesha B. M.; Cawood, Cherie; Khanyile, David; Grobler, Anneke; Mckinnon, Lyle R.; Samsunder, Natasha; Frohlich, Janet A.; Karim, Quarraisha Abdool; Puren, Adrian; Welte, Alex; George, Gavin; Govender, Kaymarlin; Toledo, Carlos; Chipeta, Zawadi; Zembe, Lycias; Glenshaw, Mary T.; Madurai, Lorna; Deyde, Varough M.; Bere, Alfred
    Background: South Africa has over 6,000,000 HIV infected individuals and the province of KwaZulu-Natal (KZN) is the most severely affected. As public health initiatives to better control the HIV epidemic are implemented, timely, detailed and robust surveillance data are needed to monitor, evaluate and inform the programmatic interventions and policies over time. We describe the rationale and design of the HIV Incidence Provincial Surveillance System (HIPSS) to monitor HIV prevalence and incidence. Methods/Design: The household-based survey will include a sample of men and women from two sub-districts of the uMgungundlovu municipality (Vulindlela and the Greater Edendale) of KZN, South Africa. The study is designed as two sequential cross-sectional surveys of 10,000 randomly selected individuals aged 15 – 49 years to be conducted one year apart. From the cross sectional surveys, two sequential cohorts of HIV negative individuals aged 15 – 35 years will be followed-up one year later to measure the primary outcome of HIV incidence. Secondary outcomes include the laboratory measurements for pulmonary tuberculosis, sexually transmitted infections and evaluating tests for estimating population-level HIV incidence. Antiretroviral therapy (ART) access, HIV-1 RNA viral load, and CD4 cell counts in HIV positive individuals will assess the effectiveness of the HIV treatment cascade. Household and individual-level socio-demographic characteristics, exposure to HIV programmatic interventions and risk behaviours will be assessed as predictors of HIV incidence. The incidence rate ratio of the two cohorts will be calculated to quantify the change in HIV incidence between consecutive samples. In anticipation of better availability of population-level HIV prevention and treatment programmes leading to decreases in HIV incidence, the sample size provides 84 % power to detect a reduction of 30 % in the HIV incidence rate between surveys. Discussion: The results from HIPSS will provide critical data regarding HIV prevalence and incidence in this community and will establish whether HIV prevention and treatment efforts in a “ real world ” , non-trial setting have an impact on HIV incidence at a population level. Importantly, the study design and methods will inform future methods for HIV surveillance.