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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 J; Smith H; Mwamba C; Haambokoma M; Sharma A; Savory T; Musheke M; Pry J; Bolton C; Sikazwe I; Herce ME; Research Department, Social and Behavioral Science Unit, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.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 in action: lessons from an observational study of HIV prevention programming for key populations in Lusaka, Zambia.(2024-Jul) Sikazwe I; Musheke M; Chiyenu K; Ngosa B; Pry JM; Mulubwa C; Zimba M; Sakala M; Sakala M; Somwe P; Nyirenda G; Savory T; Bolton-Moore C; Herce ME; Department of Public Health Sciences, School of Medicine, University of California, Davis, California, USA.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina, USA.; Division of Infectious Diseases, Department of Medicine, University of Alabama, Birmingham, Alabama, USA.; Tithandizeni Umoyo Network, Lusaka, Zambia.; Intersex Society of Zambia, Lusaka, Zambia.; Zambia Sex Workers Alliance, Lusaka, Zambia.INTRODUCTION: Optimizing uptake of pre-exposure prophylaxis (PrEP) for individuals at risk of HIV acquisition has been challenging despite clear scientific evidence and normative guidelines, particularly for key populations (KPs) such as men who have sex with men (MSM), female sex workers (FSWs), transgender (TG) people and persons who inject drugs (PWID). Applying an iterative Programme Science cycle, building on the effective programme coverage framework, we describe the approach used by the Centre for Infectious Disease Research in Zambia (CIDRZ) to scale up PrEP delivery and address inequities in PrEP access for KP in Lusaka, Zambia. METHODS: In 2019, CIDRZ partnered with 10 local KP civil society organizations (CSOs) and the Ministry of Health (MOH) to offer HIV services within KP-designated community safe spaces. KP CSO partners led KP mobilization, managed safe spaces and delivered peer support; MOH organized clinicians and clinical commodities; and CIDRZ provided technical oversight. In December 2021, we introduced a community-based intervention focused on PrEP delivery in venues where KP socialize. We collected routine programme data from September 2019 to June 2023 using programme-specific tools and the national electronic health record. We estimated the before-after effects of our intervention on PrEP uptake, continuation and equity for KP using descriptive statistics and interrupted time series regression, and used mixed-effects regression to estimate marginal probabilities of PrEP continuity. RESULTS: Most (25,658) of the 38,307 (67.0%) Key Population Investment Fund beneficiaries were reached with HIV prevention services at community-based venues. In total, 23,527 (61.4%) received HIV testing services, with 15,508 (65.9%) testing HIV negative and found PrEP eligible, and 15,241 (98.3%) initiating PrEP. Across all programme quarters and KP types, PrEP uptake was >90%. After introducing venue-based PrEP delivery, PrEP uptake (98.7% after vs. 96.5% before, p < 0.001) and the number of initiations (p = 0.014) increased significantly. The proportion of KP with ≥1 PrEP continuation visit within 6 months of initiation was unchanged post-intervention (46.7%, 95% confidence interval [CI]: 45.7%, 47.6%) versus pre-intervention (47.2%, 95% CI: 45.4%, 49.1%). CONCLUSIONS: Applying Programme Science principles, we demonstrate how decentralizing HIV prevention services to KP venues and safe spaces in partnership with KP CSOs enabled successful community-based PrEP delivery beyond the reach of traditional facility-based services.Item Programme science methodologies and practices that address "FURRIE" challenges: examples from the field.(2024-Jul) Hargreaves JR; Baptiste S; Bhattacharjee P; Cowan FM; Herce ME; Lauer K; Sikazwe I; Geng E; CeSHHAR, Harare, Zimbabwe.; International Treatment Preparedness Coalition, Johannesburg, South Africa.; Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, USA.; Liverpool School of Tropical Medicine, Liverpool, UK.; Partners for Health and Development in Africa, Nairobi, Kenya.; CIDRZ, Lusaka, Zambia.; Division of Infectious Diseases and Center for Dissemination and Implementation, Washington University in St. Lous, St. Louis, Missouri, USA.; Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK.; Institute for Global Public Health, University of Manitoba, Winnipeg, Manitoba, Canada.INTRODUCTION: "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 S; Potchen M; Sikazwe I; Kampondeni S; Hoffman C; Bearden D; Kalungwana L; Musonda N; Mathews M; Mwenechanya M; Dallah I; Johnson B; Bositis C; Huang J; Birbeck GL; Department of Neurology, Pediatric, University of Rochester, Rochester, New York.; Center for Infectious Diseases Research in Zambia (CIDRZ), Lusaka, Zambia.; TrialSpark, New York, New York.; University of Rochester School of Medicine, Rochester, New York.; Department of Neurology, Epilepsy, University of Rochester, Rochester, New York.; Department of Family and Community Medicine, University of California, San Francisco, San Francisco, California.; University Teaching Hospital-Children's Hospital, Lusaka, Zambia.; Department of Imaging Sciences, University of Rochester, Rochester, New York. Electronic address: sarahmohajeri29@gmail.com.; Mpingwe Clinic, Blantyre, Malawi.; Department of Imaging Sciences, University of Rochester, Rochester, New York.; Department of Psychology, University of Zambia, Lusaka, Zambia.; Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York.; Department of Radiology, Michigan State University, East Lansing, Michigan.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 Reimagining HIV prevention with artificial intelligence.(2025-Jun-11) Ratevosian J; Reid M; Ni Z; Mendonca R; Eakle R; Johnson C; Sikazwe I; Ndirangu M; Baptiste S; Bekker LG; Desmond Tutu Health Foundation, Cape Town, South Africa.; International Treatment Preparedness Coalition (ITPC), Johannesberg, South Africa.; Washington, DC, USA.; Duke University, Washington 20001, DC, USA. Electronic address: jirair.ratevosian@duke.edu.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Yale University, New Haven, CT, USA.; World Health Organization, Geneva, Switzerland.; Audere Africa, Seattle, WA, USA.; Amref Health Africa, Nairobi, Kenya.; University of California, San Francisco (UCSF), San Francisco, CA, USA.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 N; Shimbo T; Miyano S; Sikazwe I; Mwango A; Ghidinelli MN; Syakantu G; Pan American Health Organization, Washington, D.C., United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; National Center for Global Health and Medicine, Tokyo, Japan.; Ministry of Health, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)BACKGROUND: 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 COVID-19 vaccine uptake and associated risk factors among first antenatal care attendees in Zambia, 2021-2022: A repeated cross-sectional study.(2024) Tembo T; Somwe P; Bosomprah S; Heilmann E; Kalenga K; Moyo N; Kabamba B; Seffren V; Fwoloshi S; Rutagwera MR; Musunse M; Mwiinga L; Gutman JR; Hines JZ; Sikazwe I; Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Analysis Unit, Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Reproductive, Maternal, Newborn and Child Health (RMNCH), Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Department of Biostatistics, School of Public Health, University of Ghana, Accra, Accra.; Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.; Centers for Disease Control and Prevention, Lusaka, Zambia.; PATH, Lusaka, Zambia.; Strategic Information Unit, Center for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; University Teaching Hospital, Ministry of Health, Lusaka, Zambia.Pregnant 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 Cognitive impairment and psychiatric morbidity in HIV+ Zambians with new-onset seizure.(2014-Dec) Kalungwana L; Elafros MA; Siddiqi OK; Bositis CM; Sikazwe I; Koralnik IJ; Theodore WH; Birbeck GL; Department of Psychology, University of Zambia, Lusaka, Zambia; International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia; Division of NeuroVirology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Greater Lawrence Family Health Center, Lawrence, Massachusetts; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; Department of Neurology, Epilepsy Division, University of Rochester, Rochester, New York; Chikankata Epilepsy Care Team, Mazabuka, Zambia.; Department of Psychology, University of Zambia, Lusaka, Zambia; International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; College of Human Medicine, Michigan State University, East Lansing, Michigan; Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia; Division of NeuroVirology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Greater Lawrence Family Health Center, Lawrence, Massachusetts; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland; Department of Neurology, Epilepsy Division, University of Rochester, Rochester, New York; Chikankata Epilepsy Care Team, Mazabuka, Zambia gretchen_birbeck@urmc.rochester.edu.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)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.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 SD; Chi BH; Kusanthan T; Chilopa B; Levy J; Sikazwe I; Mwaba P; Stringer JS; Zambian Central Statistical Office, Lusaka, Zambia .; Department of Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, England .; University of Zambia, Lusaka, Zambia .; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia .; Zambian Ministry of Health, Lusaka, Zambia .; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)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 Neuroimaging abnormalities and seizure recurrence in a prospective cohort study of zambians with human immunodeficiency virus and first seizure.(2014-Oct-23) Potchen MJ; Siddiqi OK; Elafros MA; Koralnik IJ; Theodore WH; Sikazwe I; Kalungwana L; Bositis CM; Birbeck GL; Epilepsy Division, Department of Neurology, University of Rochester , NY, USA ; Chikankata Epilepsy Care Team , Mazabuka, Zambia.; Centre for Infectious Disease Research in Zambia , Lusaka, Zambia.; Clinical Epilepsy Section, United States National Institutes of Health , Bethesda, MD, USA.; Greater Lawrence Family Health Center , Lawrence, MA, USA.; Neuroradiology Division Department of Imaging Sciences, University of Rochester , NY, USA.; College of Human Medicine, Michigan State University , East Lansing, MI, USA.; Department of Internal Medicine, University of Zambia , Lusaka, Zambia ; Division of NeuroVirology, Beth Israel Deaconess Medical Center , Boston, MA, USA.; Division of NeuroVirology, Beth Israel Deaconess Medical Center , Boston, MA, USA.; Department of Psychology, University of Zambia , Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)In HIV-positive individuals with first seizure, we describe neuroimaging findings, detail clinical and demographic risk factors for imaging abnormalities, and evaluate the relationship between imaging abnormalities and seizure recurrence to determine if imaging abnormalities predict recurrent seizures. Among 43 participants (mean 37.4 years, 56% were male), 16 (37%) were on antiretroviral drugs, 32 (79%) had advanced HIV disease, and (28) 66% had multiple seizures and/or status epilepticus at enrollment. Among those with cerebrospinal fluid studies, 14/31 (44%) had opportunistic infections (OIs). During follow-up, 9 (21%) died and 15 (35%) experienced recurrent seizures. Edema was associated with OIs (odds ratio: 8.79; confidence interval: 1.03-236) and subcortical atrophy with poorer scores on the International HIV Dementia Scale) (5.2 vs. 9.3; P=0.002). Imaging abnormalities were not associated with seizure recurrence or death (P>0.05). Seizure recurrence occurred in at least a third and over 20% died during follow-up. Imaging was not predictive of recurrent seizure or death, but imaging abnormalities may offer additional diagnostic insights in terms of OI risk and cognitive impairment.