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Item Genetic diversity in L1 ORF of human papillomavirus in women with cervical cancer with and without human immunodeficiency virus in Botswana and Kenya(Springer, 2022-01-27) Tawe, Leabaneng; Choga, Wonderful T.; Paganotti, Giacomo M.; Bareng, Ontlametse T.; Ntereke, Tlhalefo D.; Ramatlho, Pleasure; Ditshwanelo, Doreen; Gaseitsiwe, Simani; Kasvosve, Ishmael; Ramogola-Masire, Doreen; Orang’o, Omenge E.; Robertson, Erle; Zetola, Nicola; Moyo, Sikhulile; Grover, Surbhi; Ermel , Aaron C.; Medicine, School of MedicineBackground The variation of human papillomavirus (HPV) genotypes shapes the risks of cervical cancer and these variations are not well defined in Africa. Nucleotide changes within the L1 gene, nucleotide variability, and phylogeny were explored in relation to HIV in samples from Botswana and Kenya. Methods A total of 98 HPV-positive cervical samples were sequenced to identify different HPV variants. Phylogenetic inferences were used to determine HPV genotypes and investigate the clustering of sequences between women living with HIV (WLWHIV) and -women not living with HIV (WNLWHIV). Results Out of 98 generated sequences, 83.7% (82/98) participants had high-risk (HR) HPV genotypes while 16.3% (16/98) had low-risk (LR) HPV genotypes. Among participants with HR-HPV genotypes, 47.6% (39/82) were coinfected with HIV. The prevalence of HR-HPV genotypes was statistically higher in the Botswana population compared to Kenya (p-value < 0.001). Multiple amino acid mutations were identified in both countries. Genetic diversity differed considerably among WLWHIV and WNLWHIV. The mean pairwise distances between HPV-16 between HIV and HIV/HPV as well as for HPV-18 were statistically significant. Six (6) new deleterious mutations were identified in the HPV genotypes based on the sequencing of the L1 region, HPV-16 (L441P, S343P), HPV-18 (S424P), HPV-45 (Q366H, Y365F), and HPV-84 (F458L). The majority of the patients with these mutations were co-infected with HIV. Conclusions Genomic diversity and different genomic variants of HPV sequences were demonstrated. Candidate novel mutations within the L1 gene were identified in both countries which can be further investigated using functional assays.Item "We did not know what was wrong"-Barriers along the care cascade among hospitalized adolescents with HIV in Gaborone, Botswana(Public Library of Science, 2018-04-09) Enane, Leslie A.; Mokete, Keboletse; Dipesalema, Joel; Daimari, Rahul; Tshume, Ontibile; Anabwani, Gabriel; Mazhani, Loeto; Steenhoff, Andrew P.; Lowenthal, Elizabeth D.; Pediatrics, School of MedicineHigh mortality among adolescents with HIV reflects delays and failures in the care cascade. We sought to elucidate critical missed opportunities and barriers to care among adolescents hospitalized with HIV at Botswana's tertiary referral hospital. We enrolled all HIV-infected adolescents (aged 10-19 years) hospitalized with any diagnosis other than pregnancy from July 2015 to January 2016. Medical records were reviewed for clinical variables and past engagement in care. Semi-structured interviews of the adolescents (when feasible) and their caregivers explored delays and barriers to care. Twenty-one eligible adolescents were identified and 15 were enrolled. All but one were WHO Clinical Stage 3 or 4. Barriers to diagnosis included lack of awareness about perinatal HIV infection, illness or death of the mother, and fear of discrimination. Barriers to adherence to antiretroviral therapy included nondisclosure, isolation, and mental health concerns. The number of hospitalized HIV-infected adolescents was lower than expected. However, among those hospitalized, the lack of timely diagnosis and subsequent gaps in the care cascade elucidated opportunities to improve outcomes and quality of life for this vulnerable group.