Browsing by Author "Lebina, Limakatso"

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    Open Access
    Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue
    (2022-06-16) Else, Laura; Penchala, Sujan D; Pillay, Azure-Dee; Seiphetlo, Thabiso B; Lebina, Limakatso; Callebaut, Christian; Minhas, Suks; Morley, Roland; Rashid, Tina; Martinson, Neil; Fox, Julie; Khoo, Saye; Herrera, Carolina
    Background: HIV-1 pre-exposure prophylaxis (PrEP) has focused predominantly on protective efficacy in receptive sex, with limited research on the dosing requirements for insertive sex. We pre-clinically assessed the ex vivo pharmacokinetic–pharmacodynamic (PK–PD) profile of tenofovir (TFV) and tenofovir alafenamide (TAF) in foreskin tissue. Methods: Inner and outer foreskin explants were exposed to serial dilutions of TFV or TAF prior to addition of HIV-1BaL at a high (HVT) or a low viral titer (LVT). Infection was assessed by measurement of p24 in foreskin culture supernatants. TFV, TAF and TFV–diphosphate (TFV–DP) concentrations were measured in tissues, culture supernatants and dosing and washing solutions. Results: Dose–response curves were obtained for both drugs, with greater potency observed against LVT. Inhibitory equivalency mimicking oral dosing was defined between 1 mg/mL of TFV and 15 µg/mL of TAF against HVT challenge. Concentrations of TFV–DP in foreskin explants were approximately six-fold higher after ex vivo dosing with TAF than with TFV. Statistically significant negative linear correlations were observed between explant levels of TFV or TFV–DP and p24 concentrations following HVT. Conclusions: Pre-clinical evaluation of TAF in foreskin explants revealed greater potency than TFV against penile HIV transmission. Clinical evaluation is underway to support this finding.
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    Open Access
    Process evaluation of implementation fidelity of the integrated chronic disease management model in two districts, South Africa
    (2019-12-16) Lebina, Limakatso; Alaba, Olufunke; Ringane, Ashley; Hlongwane, Khuthadzo; Pule, Pogiso; Oni, Tolu; Kawonga, Mary
    Abstract Background The Integrated Chronic Disease Management (ICDM) model has been implemented in South Africa to enhance quality of clinical services in Primary Healthcare (PHC) clinics in a context of a high prevalence of chronic conditions and multi-morbidity. This study aimed to assess the implementation fidelity (adherence to guidelines) of the ICDM model. Methods A cross-sectional study in 16 PHC clinics in two health districts in South Africa: Dr. Kenneth Kaunda (DKK) and West Rand (WR). A fidelity assessment tool with 89 activities and maximum score of 158 was developed from the four interrelated ICDM model components: facility re-organization, clinical supportive management, assisted self-management and strengthening of support systems. Value stream mapping of patient flow was conducted to analyse waiting time and identify operational inefficiencies. ICDM items were scored based on structured observations, facility document reviews and structured questionnaires completed by healthcare workers. Fidelity scores were summarized using medians and proportions and compared by facilities and districts using Chi-Square and Kruskal Wallis test. Results The monthly patient headcount over a six-month period in these 16 PHC clinics was a median of 2430 (IQR: 1685–2942) individuals over 20 years. The DKK district had more newly diagnosed TB patients per month [median 5.5 (IQR: 4.00–9.33) vs 2.0 (IQR: 1.67–2.92)], and fewer medical officers per clinic [median 1 (IQR: 1–1) vs 3.5 (IQR:2–4.5)] compared to WR district. The median fidelity scores in both districts for facility re-organization, clinical supportive management, assisted self-management and strengthening of support systems were 78% [29/37, IQR: 27–31)]; 77% [30/39 (IQR: 27–34)]; 77% [30/39 (IQR: 28–34)]; and 80% [35/44 (IQR: 30–37)], respectively. The overall median implementation fidelity of the ICDM model was 79% (125/158, IQR, 117–132); WR was 80% (126/158, IQR, 123–132) while DKK was 74% (117/158, IQR, 106–130), p = 0.1409. The lowest clinic fidelity score was 66% (104/158), while the highest was 86% (136/158). A patient flow analysis showed long (2–5 h) waiting times and one stream of care for acute and chronic services. Conclusion There was some variability of scores on components of the ICDM model by PHC clinics. More research is needed on contextual adaptations of the model.