Background In order to protect health workers from SARS-CoV-2, there is need to characterise the different types of patient facing health workers. Our first aim was to determine both the infection and seroprevalence of SARS-COV-2 in health workers. Our second aim was to evaluate the occupational and demographic predictors of seropositivity to inform the country’s infection prevention and control (IPC) strategy. Methods and principal findings We invited 713 staff members at 24 out of 35 health facilities in the City of Bulawayo in Zimbabwe. Compliance to testing was defined as the willingness to uptake COVID-19 testing by answering a questionnaire and providing samples for both antibody testing and PCR testing. SARS-COV-2 antibodies were detected using a rapid diagnostic test kit and SAR-COV-2 infection was determined by real-time (RT)- PCR. Of the 713 participants, 635(89%) consented answering the questionnaire and providing blood sample for antibody testing while 560 (78.5%) agreed to provide nasopharyngeal swabs for the PCR COVID-19 testing. Of the 635 people (aged 18–73) providing a blood sample 39.1% reported a history of past COVID-19 symptoms while 14.2% reported having current symptoms of COVID-19. The most-prevalent co-morbidity among this group was hypertension (22.0%) followed by asthma (7.0%) and diabetes (6.0%). The SARS-CoV-2 sero-prevalence was 8.9%. Of the 560 participants tested for SARS-CoV-2 infection, 2 participants (0.36%) were positive for SAR-CoV-2 infection by PCR testing. None of the SARS-CoV-2 antibody positive people were positive for SAR-CoV-2 infection by PCR testing. Conclusion and interpretation In addition to clinical staff, several patient-facing health workers were characterised within Zimbabwe’s health system and the seroprevalence data indicated that previous exposure to SAR-CoV-2 had occurred across the full spectrum of patient-facing staff with nurses and nurse aides having the highest seroprevalence. Our results highlight the need for including the various health workers in IPC strategies in health centres to ensure effective biosecurity and biosafety.

Women living with HIV (WLWH) and breast cancer (BC) have worse overall survival than HIV-negative women with BC, and poor adherence to prescribed tamoxifen is known to contribute to poor survival. MethodsAmong 4,097 women diagnosed with breast cancer at six hospitals in the prospective South African Breast Cancer and HIV Outcomes (SABCHO) cohort study between July 2015 and December 2020, we focused on black women with stages I-III HRpositive breast cancer who were prescribed 20mg of adjuvant tamoxifen daily. We analyzed concentrations of tamoxifen and its metabolites using a triple quadruple mass spectrometer. We de ned non-adherence as a tamoxifen level < 60ng/mL after 3 months of daily tamoxifen use. We compared tamoxifen-related side effects, and concurrent medication use among women with and without HIV and developed multivariable logistic regression models of tamoxifen non-adherence. ResultsAmong 369 subjects, 78 (21.1%) were WLWH and 291 (78.9%) were HIV-negative. After a median (interquartile range) time of 13.0 (6.2-25.2) months since tamoxifen initiation, 208 (56.4%) women were non-adherent to tamoxifen. Women < 40 years of age were more likely to be non-adherent than women > 60 years (73.4% vs 52.6%, odds ratio (OR) = 2.49, 95% con dence interval (CI) = 1.26-4.94); likewise, WLWH (70.5% vs 52.6%, OR = 2.16, 95% CI = 1.26-3.70) than HIV-negative women. In an adjusted model WLWH had twice the odds of non-adherence to tamoxifen, compared to HIV-negative women (OR = 2.40, 95% CI = 1.11-5.20). ConclusionHigh rates of non-adherence to adjuvant tamoxifen may limit the overall survival of black South African women with HR-positive breast cancer, especially among WLWH.

Clinical outcomes of tamoxifen (TAM) treatment show wide interindividual variability. Comedications and genetic polymorphisms of enzymes involved in TAM metabolism contributes to this variability. Drug-drug and drug-gene interactions have seldom been studied in African Black populations. We evaluated the effects of commonly coadministered medicines on TAM pharmacokinetics in a cohort of 229 South African Black female patients with hormone-receptor positive breast cancer. We also investigated the pharmacokinetic effects of genetic polymorphism in enzymes involved in TAM metabolism, including the variants CYP2D6*17 and *29, which have been mainly reported in people of African descent. TAM and its major metabolites, N-desmethyltamoxifen (NDM), 4-OHtamoxifen, and endoxifen (ENDO), were quantified in plasma using the liquid chromatography-mass spectrometry. The GenoPharm open array was used to genotype CYP2D6, CYP3A5, CYP3A4, CYP2B6, CYP2C9, and CYP2C19. Results showed that CYP2D6 diplotype and CYP2D6 phenotype significantly affected endoxifen concentration (P < 0.001 and P < 0.001). CYP2D6*17 and CYP2D6*29 significantly reduced the metabolism of NDM to ENDO. Antiretroviral therapy had a significant effect on NDM levels and the TAM/NDM and NDM/ENDO metabolic ratios but did not result in significant effects on ENDO levels. In conclusion, CYP2D6 polymorphisms affected endoxifen concentration and the variants CYP2D6*17 and CYP2D6*29 significantly contributed to low exposure levels of ENDO. This study also suggests a low risk of drug-drug interaction in patients with breast cancer on TAM.

Introduction HIV-positive women with breast cancer (BC) have worse overall survival than HIV-negative women with BC, and poor adherence to prescribed tamoxifen is known to contribute to poor survival. We, therefore, investigated the association of HIV infection with adherence to adjuvant tamoxifen among women with localized hormone receptor (HR)-positive breast cancer in South Africa. Methods Among 4,097 women diagnosed with breast cancer at six hospitals in the prospective South African Breast Cancer and HIV Outcomes (SABCHO) cohort study between July 2015 and December 2020, we focused on women with stages I-III HR-positive breast cancer who were prescribed 20mg of adjuvant tamoxifen daily for ≥3 months during the study period. We collected venous blood once from each participant during a routine clinic visit and analyzed concentrations of tamoxifen and its metabolites using a triple quadruple mass spectrometer. We defined non-adherence as a tamoxifen level &lt; 60ng/mL after 3 months of prescribed daily tamoxifen use. We compared socio-demographic, lifestyle factors, tamoxifen-related side effects, and concurrent medication use among women with and without HIV and developed multivariable logistic regression models of tamoxifen non-adherence. Results Among 369 participants, 78 (21.1%) were HIV-positive and 291 (78.9%) HIV-negative. After a median (interquartile range) time of 13.0 (6.2-25.2) months since tamoxifen initiation, the tamoxifen serum concentration ranged between 1.54 and 943.0ng/mL, with a median of 52.3ng/mL. In the full cohort, 208 women (56.4%) were non-adherent to tamoxifen; only 161 (43.6%) were adherent. Women &lt; 40 years of age were less likely to adhere to tamoxifen than women &gt;60 years (73.4% vs 52.6%, odds ratio (OR)=2.49, 95% confidence interval (CI)=1.26-4.94); likewise, HIV-positive women (70.5% vs 52.6%, OR=2.16, 95% CI=1.26-3.70) were less likely to adhere than HIV-negative women. In an adjusted model, only HIV was associated with non-adherence; HIV-positive women had twice the odds of non-adherence to tamoxifen, compared to HIV-negative women (OR=2.40, 95% CI=1.11-5.20). Conclusion Non-adherence to tamoxifen may limit the overall survival of women with HR-positive breast cancer; in our study, especially in HIV-positive women. Citation Format: Oluwatosin A Ayeni, Shingirai Chiwambutsa, Wenlong Carl Chen, Nyasha N. Kapungu, Comfort Kanji, Roslyn Thelingwani, Nivashni Murugan, Rophiwa Mathiba, Boitumelo Phakathi, Sarah Nietz, Duvern Ramiah, Daniel S. O’Neil, Judith S. Jacobson, Paul Ruff, Herbert Cubasch, Tobias Chirwa, Maureen Joffe, Collen Masimirembwa, Alfred I. Neugut. The impact of HIV on non-adherence for tamoxifen among women with breast cancer in South Africa [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-03.