Browsing by Author "Karim, Farina."
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Item Effect of HIV status and suppression on SARS-CoV-2 disease severity, vaccine response, and evolution=Umthelela wesifo sesandulela-ngculazi nokucindezelwa kwaso yi-SARS-CoV-2 ubunzima besifo, ukusebenza kwekhambi kanye nokuthuthuka.(2023) Karim, Farina.; Sigal, Alexander.; Moosa, Mahomed Yunus Suleman.Abstract SARS-CoV-2 is a global pandemic that has infected 672,115,430 people globally (https://coronavirus.jhu.edu/map.html, accessed 08.02.2023). SARS-CoV-2 is continuously evolving, and new variants pose a continuous threat to curbing this pandemic. Simultaneously, South Africa still struggles to control and manage an enduring HIV pandemic. The synergistic interplay between these two pandemics has necessitated an understanding of how these two viruses interact with each other to tailor an intervention. This thesis investigated the effect of SARS-CoV-2 infection on disease dynamics, differential disease outcomes, vaccine response, as well as SARSCoV- 2 evolution in people living with HIV (PLWH) with different levels of HIV suppression and differing HIV suppression history. The first study investigated the difference in disease severity amongst PLWH in the first and second infection waves in South Africa. COVID-19. Thereafter, we explored persistent SARS-CoV-2 infection in immunocompromised individuals and intra-host evolution in a case study of a participant with advanced HIV infection. Here, we illustrated that advanced HIV disease may lead to prolonged SARS-CoV-2 infection and shedding of infectious virus and results in intra-host evolution of variant mutations, making intra-host evolution in advanced HIV individuals a particular concern within the South African context. Finally, we observed that effectively controlling HIV through ART facilitates SARS-CoV-2 clearance. The last study widened the observations to five participants with advanced HIV disease and showed that vaccination does induce a potent neutralizing antibody response in this group, but only if HIV viremia is first effectively suppressed with antiretroviral therapy. These findings highlight the importance of suppressing HIV infection in eliciting an effective immune response against, and preventing evolution of SARS-CoV-2. Iqoqa I-SARS-CoV-2 yisifo esesigulise umhlaba wonke sase sigulisa inani elingama 672,115,430 abantu emhlabeni jikelele (https://coronavirus.jhu.edu/map.html, accessed 08.02.2023). I-SARS-CoV-2 isaqhubeka nokusabalala kanti izinhlobo zayo ezinye zisaqhubeka nokuba yingozi ukuba isifo singanqandeka. Khona-manjalo, iNingizimu Afrikha isathwele kanzima ukulawula isifo sesandulela-ngculazi. Ukuthelelana nokuxhumana phakathi kwalezi zifo kwenze kwanesidingo sokuqonda ukuthi zidlelana kanjani ukwenzela ukuphuma nekhambi. Lolu cwaningo lucwaninge umthelela we SARS-CoV-2 nezinkinga ezikhona ngenxa yazo, imiphumela ehlukene yesifo, ukusebenza kwekhambi, kanjalo nokukhula kwe SARS-CoV-2 ebantwini abaphila naso lesi sifo bebe benesandulela-ngculazi benezinga lesandulela-ngculazi elehlukile kanye nomlando owehlukile. Ucwaningo lokuqala lucubungule umehluko wesankahlu sesifo ezifweni ze-PLWH esiwombeni sokuqala nesesibili salesi sifo eNingizimu Afrikha. Ngakho-ke iye yahlolwa kwalendela umthelela we-SARS-CoV-2 kubantu abanamasosha aphansi omzimba kanye nalokhu esikubiza nge-intra-host evolution ocwaningweni lwesimo kubabambi-qhaza abanesandulela-ngculazi esisezingeni eliphezulu. Lapha kutholakale ukuthi isandulela-ngculazi esisezingeni eliphezulu singaholela ekuguleni isikhathi eside uma unesifo seSARS-CoV-2 kanye nokuthola ezinye izifo ezithelelanayo kanti imiphumela ye-intra-host evolution of variant mutations, okwenza ukukhula kwe-intra-host kulabo abanesandulela-ngculazi ephezulu kusabise isimo saseNingizimu Afrikha. Isiphetho, kutholakale ukuthi ukulawula isandulela-ngculazi nge-ART kwenza iSARS-CoV-2 idambe. Ucwaningo lokugcina luveze ngokubanzi obekubukelwe kubabambiqhaza abanesandulela-ngculazi esiphezulu ngokuthi kuvele ukuthi ikhambi lenza kudambe ukugula kuleli qoqo, kodwa kuphela uma isandulela-ngculazi siqale sacindezelwa nge-antiretroviral therapy. Lemiphumela iveza ukubaluleka kokucindezelwa kwesandulela-ngculazi ukulwa kanye nokucindezela isifo seSARS-CoV-2.Item Effects of a reduced dose of Stavudine on the incidence and severity of peripheral neuropathy in HIV-infected adults in South Africa.(International Medical Press., 2011) Pahuja, Meera.; Grobler, Anna Christina.; Glesby, Marshall J.; Karim, Farina.; Parker, Gary.; Gumede, Sizwe.; Naidoo, Kogieleum.BACKGROUND—Although recent WHO guidelines recommend withdrawing stavudine (d4T) from first-line ART therapy, it remains commonly used in resource-constrained settings. In 2006, WHO recommended decreasing the dose of d4T from 40mg to 30mg to mitigate toxicities. We compared the incidence and severity of peripheral neuropathy (PN) by d4T dose in a retrospective cohort study. METHODS—Patients’ charts from an ART-naïve population at a rural clinic in KZN, South Africa were retrospectively reviewed for signs and symptoms of incident PN and were graded for severity using the DAIDs scale. Patients enrolled prior to the WHO guideline change were enrolled if they were on d4T 40mg for at least 6 months. After the guideline change all patients were initiated on d4T 30mg. RESULTS—A total of 475 patients were analyzed; 235 in the 40mg cohort (152.7 person-years [py]) and 240 in the 30mg cohort (244.7py). Incidence of peripheral neuropathy was 90.4/100 py (95% CI:75.9–106.8) in the 40mg cohort versus 40.5/100py (95% CI:32.9–49.3) in the 30mg group (incidence rate ratio [IRR]=0.45, p<0.0001). There was no difference in proportion of severe peripheral neuropathy cases (grade 3/4) between the cohorts; 8.3% in the 40mg group and 8.9% in the 30mg group (p=1.0). In a multivariate analysis risk of peripheral neuropathy was associated with increasing age (HR=1.65 95% CI:1.24–2.19), 40 mg dose (HR=2.1, 95% CI:1.61–2.74) and concurrent tuberculosis therapy (HR= 1.41 95% CI:1.06–1.87). CONCLUSION—Incidence of peripheral neuropathy in the 40mg cohort was extremely high and though lower in the 30mg cohort, the rate was nonetheless unacceptably high.Item An exploration of the concerns and motivations of community caregivers working with children in adversity.(2010) Karim, Farina.; Killian, Beverley Janet.The deadly HIV/AIDS pandemic is one of the major developmental challenges facing our nation. Community caregivers (CCGs) play a significant role in addressing the psychosocial needs of orphan and vulnerable children (OVC); however, little attention has been paid to the work and experiences of CCGs. In an endeavour to increase our understanding of their lived experiences, this research qualitatively explored the concerns and motivations experienced by CCGs who work on a daily basis with children in circumstances of extreme adversity, specifically those affected by HIV/AIDS in South Africa. This study draws on the ecological theory of Bronfrenbrenner (1979) to provide a conceptual framework in which to consider the working circumstances of CCGs. Methodologically, focus group discussions were used as the primary source of data collection. Focus groups were conducted with CCGs from three different non-governmental organisations (NGOs) who provide psychosocial support to children affected by HIV/AIDS. The research found that CCGs are passionate about providing holistic care to the children, families and communities in which they work and they experience a variety of concerns about the way in which services are provided and how funding agendas drive the nature of the work and the manner of monitoring and evaluation. They also experience joy and satisfaction in what they do. Limitations and suggestions for future studies are noted, with the aim being for NGOs to acknowledge the concerns and motives and to develop and implement programmes to support staff, and maintain the resilience needed for CCGs to be even more effective in contributing towards providing meaningful services in the difficult circumstance in which they work.Item High rates of tuberculosis in patients accessing HAART in rural South Africa.(Lippincott Williams & Wilkins., 2014) Naidoo, Kogieleum.; Abdool Karim, Quarraisha.; Bhushan, Ambika.; Naidoo, Kasavan.; Yende-Zuma, Fortunate Nonhlanhla.; Mchunu, Patricia K.; Fröhlich, Janet Ann.; Karim, Farina.; Upfold, Michele.; Kocheleff, Paul.; Abdool Karim, Salim Safurdeen.Background: The challenge of early tuberculosis (TB) infection among rural patients accessing highly active antiretroviral therapy (HAART) in a resource-limited setting with high HIV and TB burden has not been fully quantified. Methods: This is a retrospective study nested within a prospective study of 969 patients consecutively initiated onto HAART at the CAPRISA AIDS Treatment programme in rural KwaZulu-Natal between January 2007 and December 2010. Patients were screened for clinical symptoms consistent with TB using a standardized checklist, and routine clinical investigations that included sputum microscopy and chest x-ray diagnosis. Results: Of 969 HIV-infected patients initiated on HAART, 173 [17.9%; 95% confidence interval (CI): 15.5 to 20.4] had active TB at HAART initiation. TB incidence rates were 3-fold higher in the first 3 months (early incident TB) after HAART initiation [11.5/100 person years (py); 95% CI: 7.1 to 17.5] compared with 4–24 months (late incident TB) post-HAART initiation (3.2/100 py; 95% CI: 2.2 to 4.5; incidence rate ratio: 3.6; 95% CI: 2.0 to 6.4; P , 0.001). Immune status of patients at HAART initiation did not impact TB incidence rates in patients with CD4+ counts of ,50 (5.3/100) and .200 (4.9/100 py; P = 0.81) cells per cubic millimeter. CD4+ count gains achieved 12 months post-HAART initiation were significantly different in patients with early incident TB versus late incident TB; P = 0.03. Conclusions: Rural HIV treatment programmes in TB-endemic settings experience high rates of TB irrespective of immunologic status of patients at HAART initiation, or duration on HAART.Item A novel reporter phage to detect tuberculosis and rifampin resistance in a high-HIV-burden population.(American Society for Microbiology., 2015) O’Donnell, Max Roe.; Pym, Alexander S.; Jain, Paras.; Munsamy, Vanisha.; Wolf, Allison.; Karim, Farina.; Jacobs, William R.; Larsen, Michelle H.Abstract available in pdf.