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The CIDRZ Research Repository serves as an open-access archive for peer-reviewed publications, conference papers, and other scholarly outputs from CIDRZ researchers. Our goal is to promote the dissemination of knowledge and support evidence-based public health initiatives.
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Item An exploration of multi-level factors affecting routine linkage to HIV care in Zambia's PEPFAR-supported treatment program in the treat all era.(2024) Chipungu, Jenala; Smith, Helene; Mwamba, Chanda; Haambokoma, Mwiza; Sharma, Anjali; Savory, Theodora; Musheke, Maurice; Pry, Jake; Bolton, Carolyn; Sikazwe, Izukanji; Herce, Michael E.Multiple steps from HIV diagnosis to treatment initiation and confirmed engagement with the health system are required for people living with HIV to establish full linkage to care in the modern treat all era. We undertook a qualitative study to gain an in-depth understanding of the impeding and enabling factors at each step of this linkage pathway. In-depth interviews were conducted with fifty-eight people living with HIV recruited from ten routine HIV care settings supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) in Lusaka, Zambia. Using a semi-structured interview guide informed by an established conceptual framework for linkage to care, questions explored the reasons behind late, missed, and early linkage into HIV treatment, as well as factors influencing the decision to silently transfer to a different clinic after an HIV diagnosis. We identified previously established and intersecting barriers of internal and external HIV-related stigma, concerns about ART side effects, substance use, uncertainties for the future, and a perceived lack of partner and social support that impeded linkage to care at every step of the linkage pathway. However, we also uncovered newer themes specific to the current test and treat era related to the rapidity of ART initiation and insufficient patient-centered post-test counseling that appeared to exacerbate these well-known barriers, including callous health workers and limited time to process a new HIV diagnosis before treatment. Long travel distance to the clinic where they were diagnosed was the most common reason for silently transferring to another clinic for treatment. On the other hand, individual resilience, quality counseling, patient-centered health workers, and a supportive and empathetic social network mitigated these barriers. These findings highlight potential areas for strengthening linkage to care and addressing early treatment interruption and silent transfer in the test and treat era in Zambia.Item Programme science methodologies and practices that address "FURRIE" challenges: examples from the field.(2024-Jul) Hargreaves, James R.; Baptiste, Solange; Bhattacharjee, Parinita ; Cowan, Frances M.; Herce, Michael E.; Lauer, Krista; Sikazwe, Izukanji ; Geng, ElvinINTRODUCTION: "Programme science" deploys scientific methods to address questions that are a priority to support the impact of public health programmes. As such, programme science responds to the challenges of making such studies: (1) feasible to undertake, (2) useful, (3) rigorous, (4) real-world-relevant, (5) informative, and undertaken by (6) equitable partnerships. The acronym "FURRIE" is proposed to describe this set of six challenges. This paper discusses selected HIV/STI (sexually transmitted infection) programme science case studies to illustrate how programme science rises to the FURRIE challenges. DISCUSSION: One way in which programme science is made more feasible is through the analysis and interpretation of data collected through service delivery. For some questions, these data can be augmented through methods that reach potential clients of services who have not accessed services or been lost to follow-up. Process evaluation can enhance the usefulness of programme science by studying implementation processes, programme-client interactions and contextual factors. Ensuring rigour by limiting bias and confounding in the real-world context of programme science studies requires methodological innovation. Striving for scientific rigour can also have the unintended consequence of creating a gap between what happens in a study, and what happens in the "real-world." Community-led monitoring is one approach to grounding data collection in the real-world experience of clients. Evaluating complex, context-specific strategies to strengthen health outcomes in a way that is informative for other settings requires clear specification of the intervention packages that are planned and delivered in practice. Programme science provides a model for equitable partnership through co-leadership between programmes, researchers and the communities they serve. CONCLUSIONS: Programme science addresses the FURRIE challenges, thereby improving programme impact and ultimately health outcomes and health equity. The adoption and adaptation of the types of novel programme science approaches showcased here should be promoted within and beyond the HIV/STI field.Item Brain Imaging in New-Onset Seizure of Children Living With Human Immunodeficiency Virus in Zambia.(2024-Oct) Mohajeri, Sarah; Potchen, Michael; Sikazwe, Izukanji ; Kampondeni, Samuel; Hoffman, Colleen; Bearden, David; Kalungwana, Lisa; Musonda, Namwiya ; Mathews, Manoj; Mwenechanya, Musaku; Dallah, IIfunanya; Johnson, Brent; Bositis, Christopher ; Huang, Jessie; Birbeck, Gretchen L.BACKGROUND: There are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure. METHODS: In this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered. RESULTS: Nineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9). CONCLUSIONS: Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment.Item COVID-19 vaccine uptake and associated risk factors among first antenatal care attendees in Zambia, 2021-2022: A repeated cross-sectional study.(2024) Tembo, Tannia; Somwe, Paul; Bosomprah, Samuel; Heilmann, Elizabeth; Kalenga, Kalubi; Moyo, Nyembezi; Kabamba, Bupe; Seffren, Victoria; Fwoloshi, Sombo; Rutagwera, Marie-Reine ; Musunse, Maximillian; Mwiinga, Linos; Gutman, Julie R.; Hines, Jonas Z.; Sikazwe, IzukanjiPregnant women are considered a high-risk group for COVID-19, and a priority for vaccination. Routine antenatal care (ANC) provides an opportunity to track trends and factors associated with vaccine uptake. We sought to evaluate COVID-19 vaccine uptake among pregnant women attending ANC and assess the factors associated with vaccine in Zambia. We conducted a repeated cross-sectional study in 39 public health facilities in four districts in Zambia from September 2021 to September 2022. Pregnant women who were aged 15-49 years were enrolled during their first ANC visit. Every month, ~20 women per facility were interviewed during individual HIV counseling and testing. We estimated vaccine uptake as the proportion of eligible participants who self-reported having received the COVID-19 vaccine. A total of 9,203 pregnant women were screened, of which 9,111 (99%) were eligible and had vaccination status. Of the 9,111 included in the analysis, 1,818 (20%) had received the COVID-19 vaccine during the study period, with a trend of increasing coverage with time (0.5% in September 2020, 27% in September 2022). Conversely, 3,789 (42%) reported not being offered a COVID-19 vaccine. We found that women aged 40-49 years, had no education or attained some primary school education, were not employed, and had prior COVID-19 infection were significantly associated with vaccine uptake. COVID-19 vaccine uptake among pregnant women was lower than estimates from the general population (27% across the four districts in September 2022), pointing to missed opportunities to protect this high-risk group. ANC visits were a viable point for conducting COVID-19 surveillance. Incorporating the vaccine as part of the routine ANC package might increase coverage in this group.Item Effect of a multicomponent, person-centred care intervention on client experience and HIV treatment outcomes in Zambia: a stepped-wedge, cluster-randomised trial.(2025-Jan) Sikombe, Kombatende; Mody, Aaloke; Goss, Charles W.; Simbeza, Sandra; Beres, Laura K.; Pry, Jake M.; Eshun-Wilson, Ingrid; Sharma, Anjali; Mukamba, Njekwa; Mulenga, Lloyd B.; Rice, Brian; Mutale, Jacob; Zulu, Alida D.; Mulabe, Musunge; Hargreaves, James; Bolton-Moore, Carolyn; Holmes, Charles B.; Sikazwe, Izukanji ; Geng, Elvin H.BACKGROUND: Recipients of health services value not only convenience but also respectful, kind, and helpful providers. To date, research to improve person-centred HIV treatment has focused on making services easier to access (eg, differentiated service delivery) rather than the interpersonal experience of care. We developed and evaluated a person-centred care (PCC) intervention targeting practices of health-care workers. METHODS: Using a stepped-wedge, cluster-randomised design, we randomly allocated 24 HIV clinics stratified by size in Zambia into four groups and introduced a PCC intervention that targeted caring aspects of the behaviour of health-care workers in one group every 6 months. The intervention entailed training and coaching for health-care workers on PCC practices (to capacitate), client experience assessment with feedback to facilities (to create opportunities), and small performance-based incentives (to motivate). In a probability sample of clients who were pre-trained on a client experience exit survey and masked to facility intervention status, we evaluated effects on client experience by use of mean score change and also proportion with poor encounters (ie, score of ≤8 on a 12-point survey instrument). We examined effects on missed visits (ie, >30 days late for next scheduled encounter) in all groups and retention in care at 15 months in group 1 and group 4 by use of electronic health records. We assessed effects on treatment success at 15 months (ie, HIV RNA concentration <400 copies per mL or adjudicated care status) in a prospectively enrolled subset of clients from group 1 and group 4. We estimated treatment effects with mixed-effects logistic regression, adjusting for sex, age, and baseline care status. This trial is registered at the Pan-African Clinical Trials Registry (202101847907585), and is completed. FINDINGS: Between Aug 12, 2019, and Nov 30, 2021, 177 543 unique clients living with HIV made at least one visit to one of the 24 study clinics. The PCC intervention reduced the proportion of poor visits based on exit surveys from 147 (23·3%) of 632 during control periods to 33 (13·3%) of 249 during the first 6 months of intervention, and then to eight (3·5%) of 230 at 6 months or later (adjusted risk difference [aRD] for control vs ≥6 months intervention -16·9 percentage points, 95% CI -24·8 to -8·9). Among all adult scheduled appointments, the PCC intervention reduced the proportion of missed visits from 90 593 (25·3%) of 358 741 during control periods to 40 380 (22·6%) of 178 523 in the first 6 months, and then 52 288 (21·5%) of 243 350 at 6 months or later (aRD for control vs the intervention -4·2 percentage points, 95% CI -4·8 to -3·7). 15-month retention improved from 33 668 (80·2%) of 41 998 in control to 35 959 (83·6%) of 43 005 during intervention (aRD 5·9 percentage points, 95% CI 0·6 to 11·2), with larger effects in clients newly starting treatment (aRD 12·7 percentage points, 1·4 to 23·9). We found no effect on treatment success (based on viral load) in a nested subcohort (379 [83·7%] of 453 in the control phase vs 402 [83·8%] of 480 in the intervention phase; aRD 0·9 percentage points, -5·4 to 7·2). INTERPRETATION: Improving the caring aspects of health-care worker behaviour is feasible in public health settings, enhances client experience, reduces missed appointments, and increases retention. FUNDING: The Bill & Melinda Gates Foundation.Item Comparative outcomes of tenofovir-based and zidovudine-based antiretroviral therapy regimens in Lusaka, Zambia.(2011-Dec-15) Chi, Benjamin H.; Mwango, Albert; Giganti, Mark J.; Sikazwe, Izukanji ; Moyo, Crispin; Schuttner, Linnaea; Mulenga, Lloyd B.; Bolton-Moore, Carolyn; Chintu, Namwinga T.; Sheneberger, Robert; Stringer, Elizabeth M.; Stringer, Jeffrey S.BACKGROUND: Although tenofovir (TDF) is a common component of antiretroviral therapy (ART), recent evidence suggests inferior outcomes when it is combined with nevirapine (NVP). METHODS: We compared outcomes among patients initiating TDF + emtricitabine or lamivudine (XTC) + NVP, TDF + XTC + efavirenz (EFV), zidovudine (ZDV) + lamuvidine (3TC) + NVP, and ZDV + 3TC + EFV. We categorized drug exposure by initial ART dispensation by a time-varying analysis that accounted for drug substitutions and by predominant exposure (>75% of drug dispensations) during an initial window period. Risks for death and program failure were estimated using Cox proportional hazard models. All regimens were compared with ZDV + 3TC + NVP. RESULTS: Between July 2007 and November 2010, 18,866 treatment-naive adults initiated ART: 18.2% on ZDV + 3TC + NVP, 1.8% on ZDV + 3TC + EFV, 36.2% on TDF + XTC + NVP, and 43.8% on TDF + XTC + EFV. When exposure was categorized by initial prescription, patients on TDF + XTC + NVP [adjusted hazard ratio (AHR): 1.45; 95% confidence interval (CI): 1.03 to 2.06] had a higher post-90-day mortality. TDF + XTC + NVP was also associated with an elevated risk for mortality when exposure was categorized as time-varying (AHR: 1.51; 95% CI: 1.18 to 1.95) or by predominant exposure over the first 90 days (AHR: 1.91, 95% CI: 1.09 to 3.34). However, these findings were not consistently observed across sensitivity analyses or when program failure was used as a secondary outcome. CONCLUSION: TDF + XTC + NVP was associated with higher mortality when compared with ZDV + 3TC + NVP but not consistently across sensitivity analyses. These findings may be explained in part by inherent limitations to our retrospective approach, including residual confounding. Further research is urgently needed to compare the effectiveness of ART regimens in use in resource-constrained settings.Item Managing multiple funding streams and agendas to achieve local and global health and research objectives: lessons from the field.(2014-Jan-01) Holmes, Charles B.; Sikazwe, Izukanji; Raelly, Roselyne L.; Freeman, Bethany L.; Wambulawae, Inonge; Silwizya, Geoffrey; Topp, Stephanie M.; Chilengi, Roma; Henostroza, German; Kapambwe, Sharon; Simbeye, Darius; Sibajene, Sheila; Chi, Harmony; Godfrey, Katy; Chi, Benjamin H.; Bolton-Moore, CarolynMultiple funding sources provide research and program implementation organizations a broader base of funding and facilitate synergy, but also entail challenges that include varying stakeholder expectations, unaligned grant cycles, and highly variable reporting requirements. Strong governance and strategic planning are essential to ensure alignment of goals and agendas. Systems to track budgets and outputs, as well as procurement and human resources are required. A major goal of funders is to transition leadership and operations to local ownership. This article details successful approaches used by the newly independent nongovernmental organization, the Centre for Infectious Disease Research in Zambia.Item Health outcomes and cost impact of the new WHO 2013 guidelines on prevention of mother-to-child transmission of HIV in Zambia.(2014) Ishikawa, Naoko; Shimbo, Takuro; Miyano, Shinsuke; Sikazwe, Izukanji ; Mwango, Albert; Ghidinelli, Massimo N.; Syakantu, GardnerBACKGROUND: Countries are currently progressing towards the elimination of new paediatric HIV infections by 2015. WHO published new consolidated guidelines in June 2013, which now recommend either 'Antiretroviral drugs (ARVs) for women living with HIV during pregnancy and breastfeeding (Option B)' or 'Lifelong antiretroviral therapy (ART) for all pregnant and breastfeeding women living with HIV (Option B+)', while de facto phasing out Option A. This study examined health outcomes and cost impact of the shift to WHO 2013 recommendations in Zambia. METHODS: A decision analytic model was developed based on the national health system perspective. Estimated risk and number of cases of HIV transmission to infants and to serodiscordant partners, and proportions of HIV-infected pregnant women with CD4 count of ≤350 cells/mm3 to initiate ART were compared between 2010 Option A and the 2013 recommendations. Total costs of prevention of mother-to-child transmission of HIV (PMTCT) services per annual cohort of pregnant women, incremental cost-effectiveness ratio (ICER) per infection averted and quality-adjusted life-year (QALY) gained were examined. RESULTS: Our analysis suggested that the shift from 2010 Option A to the 2013 guidelines would result in a 33% reduction of the risk of HIV transmission among exposed infants. The risk of transmission to serodiscordant partners for a period of 24 months would be reduced by 72% with 'ARVs during pregnancy and breastfeeding' and further reduced by 15% with 'Lifelong ART'. The probability of HIV-infected pregnant women to initiate ART would increase by 80%. It was also suggested that while the shift would generate higher PMTCT costs, it would be cost-saving in the long term as it spares future treatment costs by preventing infections in infants and partners. CONCLUSION: The shift to the WHO 2013 guidelines in Zambia would positively impact health of family and save future costs related to care and treatment.Item Trends in all-cause mortality during the scale-up of an antiretroviral therapy programme: a cross-sectional study in Lusaka, Zambia.(2014-Oct-01) Rathod, Sujit D.; Chi, Benjamin H.; Kusanthan, Thankian; Chilopa, Batista; Levy, Jens; Sikazwe, Izukanji; Mwaba, Peter; Stringer, Jeffrey S.OBJECTIVE: To follow the trends in all-cause mortality in Lusaka, Zambia, during the scale-up of a national programme of antiretroviral therapy (ART). METHODS: Between November 2004 and September 2011, we conducted 12 survey rounds as part of a cross-sectional study in Lusaka, with independent sampling in each round. In each survey, we asked the heads of 3600 households to state the number of deaths in their households in the previous 12 months and the number of orphans aged less than 16 years in their households and investigated the heads' knowledge, attitudes and practices related to human immunodeficiency virus (HIV). FINDINGS: The number of deaths we recorded - per 100 person-years - in each survey ranged from 0.92 (95% confidence interval, CI: 0.78-1.09) in September 2011, to 1.94 (95% CI: 1.60-2.35) in March 2007. We found that mortality decreased only modestly each year (mortality rate ratio: 0.98; 95% CI: 0.95-1.00; P = 0.093). The proportion of households with orphans under the age of 16 years decreased from 17% in 2004 to 7% in 2011. The proportions of respondents who had ever been tested for HIV, had a comprehensive knowledge of HIV, knew where to obtain free ART and reported that a non-pregnant household member was receiving ART gradually increased. CONCLUSION: The expansion of ART services in Lusaka was not associated with a reduction in all-cause mortality. Coverage, patient adherence and retention may all have to be increased if ART is to have a robust and lasting impact at population level in Lusaka.Item Cognitive impairment and psychiatric morbidity in HIV+ Zambians with new-onset seizure.(2014-Dec) Kalungwana, Lisa; Elafros, Melissa A.; Siddiqi, Omar K.; Bositis, Christopher M.; Sikazwe, Izukanji; Koralnik, Igor J.; Theodore, William H.; Birbeck, Gretchen L.A prospective cohort study of new-onset seizure in people with human immunodeficiency virus (HIV) in Zambia is ongoing to determine the incidence of subsequent epilepsy and risk factors for epileptogenesis in this population. At enrollment, we evaluated this cohort for cognitive impairment and psychiatric morbidity. Over 50% of participants had cognitive impairment and significant psychiatric morbidity. Most participants had advanced HIV disease based on CD4+ T-cell count and World Health Organization stage, but we found no association between cognitive impairment or psychiatric morbidity and HIV disease staging.