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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 Programme science in action: lessons from an observational study of HIV prevention programming for key populations in Lusaka, Zambia.(2024-Jul) Sikazwe, Izukanji; Musheke, Maurice; Chiyenu, Kanema ; Ngosa, Benard; Pry, Jake M.; Mulubwa, Chama; Zimba, Martin; Sakala, Martin; Sakala, Mphatso; Somwe, Paul; Nyirenda, Goodwin; Savory, Theodora; Bolton, Carolyn; Herce, Michael E.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 Breaking barriers, changing paradigms: Africa's radical agenda for HIV sustainability.(2025) Chola, Mumbi; Robalo, Magda; Buse, Kent; Oduro-Bonsrah, Pokuaa ; Ozoemene, Jekwu; Dieng, Abdoul; Akulu, Ruth; Madzima, Bernard; Coll-Seck, Awa M.; Sheneberger, Robb; Nene, Sesupo M. ; Sikazwe, Izukanji ; Sidibe, MichelDespite significant progress in the HIV response, the sustainability of this journey is threatened by over-reliance on external support and imported and often inappropriate models. The recent sudden shifts in the United States Government's foreign aid policy have heightened the urgency for independence. Africa is at a critical point, which presents an opportunity to move from dependency on external assistance to establishing itself as a self-sustaining center of innovation and sustainable growth. Africa must reshape its approach to the HIV response by addressing the continent's over-reliance on external funding and shift towards self-sustainability and inclusiveness. For Africa to sustain its HIV response, it is critical to have African voices and leadership in the HIV response, adopt African-centric approaches in moving from silos to the integration of programme governance, ensure renewed governance and accountability frameworks, Africanizing research and development and also ensure African medicines security and sovereignty. Africa must leverage Ubuntu approaches to empowering communities, women, youth, and key and vulnerable populations, and work with community networks for service delivery. There must also be sustained HIV Programmes in Fragile and Post-conflict Settings. It is also critical to secure domestic financing through a continental approach to financing health and well-being. For Africa to realize the vision of a sustainable, African-led, and owned HIV response and health agenda, collective action is imperative. African stakeholders must fully support this agenda and claim it as their own in the spirit of Ubuntu, within the context of continental plans for transformation and revitalization. Together, we can realize the vision of the "Africa we want."Item Implementing SARS-CoV-2 routine surveillance in antenatal care in Zambia, 2021-2022: best practices and lessons learned.(2025-Feb-28) Tembo, Tannia ; Heilmann, Elizabeth; Kabamba, Bupe M.; Fwoloshi, Sombo; Kalenga, Kalubi; Chilambe, Felix; Siwinga, Mpanji; Rutagwera, Marie-Reine ; Musunse, Maximillian; Kangale, Chabu; Yingst, Samuel; Yadav, Ruchi; Savory, Theodora; Gutman, Julie R.; Sikazwe, Izukanji ; Mulenga, Lloyd B.; Bolton-Moore, Carolyn; Hines, Jonas Z.BACKGROUND: In Zambia, the true extent of SARS-CoV-2 infections is unknown because initial surveillance focused on patients with symptoms or severe disease. Antenatal sentinel surveillance had not been used to assess infection trends. The ANC COVID-19 surveillance study sought to determine SARS-CoV-2 seroprevalence and COVID-19 vaccine uptake among pregnant women. We provide insight into the study implementation, challenges encountered, best practices, and lessons learned. METHODS: A repeated cross-sectional seroprevalence survey was implemented at 39 health facilities in four districts from September 2021 to September 2022. Pregnant women aged 15-49 years were enrolled at their first antenatal care visits. An electronic questionnaire gathered demographics and other COVID-19 related information from consenting participants. A dried blood sample was collected to detect IgG antibodies using a multiplex bead assay. Seropositive results were categorized as infection, infection and vaccination or infection based on anti-RBD and anti-nucleocapsid test results. Problems and their root causes were identified as they occurred. Practical problem-solving strategies were devised, implemented, and monitored to ensure that goals were accomplished. RESULTS: In the primary analysis, 7% of the 9,221 samples collected from participants were not tested because they were missing. COVID-19 vaccine uptake of 9,111 pregnant women was assessed. Approximately 64% of participants were cumulatively seropositive for SARS-CoV-2 antibodies. Seroprevalence increased from 27.8% in September 2021 to 56.6% in July 2022. We observed an increase in vaccine coverage (0.5-27%) over time. Women aged 40-49 years old, without education and with prior COVID-19 infection were associated with higher vaccine uptake. The Delta variant of COVID-19 and the reallocation of health facilities between two partners delayed surveillance activities and increased the cost of implementation (e.g., the purchase of additional calibration and validation kits and DBS cards). Protocol deviations were attributed to the lack of experience in conducting research but, the district RAs repeatedly trained health facility staff to enhance their research knowledge. CONCLUSIONS: Incorporating SARS-CoV-2 surveillance into routine antenatal care is feasible and potentially sustainable when existing health system infrastructure, human resources, and surveillance systems are leveraged. Yet, careful planning is needed to anticipate implementation challenges and ensure high-quality data collection.Item Estimated mortality on HIV treatment among active patients and patients lost to follow-up in 4 provinces of Zambia: Findings from a multistage sampling-based survey.(2018-Jan) Holmes, Charles B.; Sikazwe, Izukanji; Sikombe, Kombatende; Eshun-Wilson, Ingrid; Czaicki, Nancy; Beres, Laura K.; Mukamba, Njekwa; Simbeza, Sandra; Bolton-Moore, Carolyn; Hantuba, Cardinal; Mwaba, Peter; Phiri, Caroline; Padian, Nancy; Glidden, David V.; Geng, ElvinBACKGROUND: Survival represents the single most important indicator of successful HIV treatment. Routine monitoring fails to capture most deaths. As a result, both regional assessments of the impact of HIV services and identification of hotspots for improvement efforts are limited. We sought to assess true mortality on treatment, characterize the extent under-reporting of mortality in routine health information systems in Zambia, and identify drivers of mortality across sites and over time using a multistage, regionally representative sampling approach. METHODS AND FINDINGS: We enumerated all HIV infected adults on antiretroviral therapy (ART) who visited any one of 64 facilities across 4 provinces in Zambia during the 24-month period from 1 August 2013 to 31 July 2015. We identified a probability sample of patients who were lost to follow-up through selecting facilities probability proportional to size and then a simple random sample of lost patients. Outcomes among patients lost to follow-up were incorporated into survival analysis and multivariate regression through probability weights. Of 165,464 individuals (64% female, median age 39 years (IQR 33-46), median CD4 201 cells/mm3 (IQR 111-312), the 2-year cumulative incidence of mortality increased from 1.9% (95% CI 1.7%-2.0%) to a corrected rate of 7.0% (95% CI 5.7%-8.4%) (all ART users) and from 2.1% (95% CI 1.8%-2.4%) to 8.3% (95% CI 6.1%-10.7%) (new ART users). Revised provincial mortality rates ranged from 3-9 times higher than naïve rates for new ART users and were lowest in Lusaka Province (4.6 per 100 person-years) and highest in Western Province (8.7 per 100 person-years) after correction. Corrected mortality rates varied markedly by clinic, with an IQR of 3.5 to 7.5 deaths per 100 person-years and a high of 13.4 deaths per 100 person-years among new ART users, even after adjustment for clinical (e.g., pretherapy CD4) and contextual (e.g., province and clinic size) factors. Mortality rates (all ART users) were highest year 1 after treatment at 4.6/100 person-years (95% CI 3.9-5.5), 2.9/100 person-years (95% CI 2.1-3.9) in year 2, and approximately 1.6% per year through 8 years on treatment. In multivariate analysis, patient-level factors including male sex and pretherapy CD4 levels and WHO stage were associated with higher mortality among new ART users, while male sex and HIV disclosure were associated with mortality among all ART users. In both cases, being late (>14 days late for appointment) or lost (>90 days late for an appointment) was associated with deaths. We were unable to ascertain the vital status of about one-quarter of those lost and selected for tracing and did not adjudicate causes of death. CONCLUSIONS: HIV treatment in Zambia is not optimally effective. The high and sustained mortality rates and marked under-reporting of mortality at the provincial-level and unexplained heterogeneity between regions and sites suggest opportunities for the use of corrected mortality rates for quality improvement. A regionally representative sampling-based approach can bring gaps and opportunities for programs into clear epidemiological focus for local and global decision makers.Item Mortality & recurrent seizure risk after new-onset seizure in HIV-positive Zambian adults.(2018-Dec-07) Elafros, Melissa A.; Johnson, Brent A.; Siddiqi, Omar K.; Okulicz, Jason F.; Sikazwe, Izukanji; Bositis, Christopher M.; Potchen, Michael J.; Koralnik, Igor J.; Theodore, William H.; Kalungwana, Lisa; Birbeck, Gretchen L.BACKGROUND: Recurrent seizure risks in HIV-positive people with new-onset seizure are largely unknown, making it challenging to offer optimal recommendations regarding antiepileptic drug (AED) initiation. Existing outcomes data is limited, and risk factor identification requires a diagnostic assessment, which is often unavailable in regions heavily effected by HIV, like sub-Saharan Africa. METHODS: HIV-positive Zambian adults with new-onset seizure were enrolled in a prospective cohort study to determine seizure recurrence and risk factors for recurrence. Seizure etiology was evaluated, and recurrent seizures and medication usage were assessed during clinic visits. Due to unexpectedly high mortality rates, predictors of death were evaluated using proportional hazards with Gray's test to compare cumulative incidence functions for recurrent seizure across groups adjusting for the competing outcome of death. RESULTS: 95 patients were enrolled (mean age 37 years, 43% female, 83% with Karnofsky > 50) and followed for a mean of 293 days (median 241 (IQR: 29-532)). At presentation, 50 (53%) were in status epilepticus. The majority (91, 85%) had advanced HIV disease and 65 (68%) were not on combined antiretroviral therapy (cART). After extensive workup, seizure etiology remained unknown in 16 (17%). Average time to cART initiation after enrollment was 61 days. During follow up, 37 (39%) died and 23 (24%) had recurrent seizure. Most deaths (25/37, 68%) occurred in the first 60 days post-index seizure. Individuals with advanced HIV were more likely to die (HR: 19.1 [95% CI: 1.1-333.4]) as were those whose seizure etiology remained unknown (HR: 2.2 [95% CI: 1.1-4.4]). Among participants that survived from enrolment to the end of data collection on 10 May 2013 (n = 58), 20 (34%) experienced recurrent seizures. CONCLUSIONS: New-onset seizure among HIV-positive Zambian adults is associated with high mortality despite good functional status prior to presentation. Advanced HIV infection and failure to identify an underlying seizure etiology are associated with greater mortality. Recurrent seizures occur in over a third of survivors within only 2 years of follow-up. This provides evidence to support AED initiation after first seizure in HIV-positive individuals with advanced HIV disease at the time of presentation though the risks of AED-cART interactions remain a concern and warrant further study.Item Operational characteristics of antiretroviral therapy clinics in Zambia: a time and motion analysis.(2019-Apr-24) Tampi, Radhika P.; Tembo, Taniya; Mukumba-Mwenechanya, Mpande; Sharma, Anjali; Dowdy, David W.; Holmes, Charles B.; Bolton-Moore, Carolyn; Sikazwe, Izukanji; Tucker, Austin; Sohn, HojoonBACKGROUND: The mass scale-up of antiretroviral therapy (ART) in Zambia has taken place in the context of limited infrastructure and human resources resulting in many operational side-effects. In this study, we aimed to empirically measure current workload of ART clinic staff and patient wait times and service utilization. METHODS: We conducted time and motion (TAM) studies from both the healthcare worker (HCW) and patient perspectives at 10 ART clinics throughout Zambia. Trained personnel recorded times for consecutive discrete activities based on direct observation of clinical and non-clinical activities performed by counselors, clinical officers, nurses, and pharmacy technicians. For patient TAM, we recruited consenting patients and recorded times of arrival and departure and major ART services utilized. Data from 10 clinics were pooled to evaluate median time per patient spent for each activity and patient duration of stay in the clinic. RESULTS: The percentage of observed clinical time for direct patient interaction (median time per patient encounter) was 43.1% for ART counselors (4 min, interquartile range [IQR] 2-7), 46.1% for nurses (3 min, IQR 2-4), 57.2% for pharmacy technicians (2 min, IQR 1-2), and 78.5% for clinical officers (3 min, IQR 2-5). Patient workloads for HCWs were heaviest between 8 AM and 12 PM with few clinical activities observed after 2 PM. The length of patient visits was inversely associated with arrival time - patients arriving prior to 8 AM spent 61% longer at the clinic than those arriving after 8 AM (277 vs. 171 min). Overall, patients spent 219 min on average for non-clinical visits, and 244 min for clinical visits, but this difference was not significant in rural clinics. In comparison, total time patients spent directly with clinic staff were 9 and 12 min on average for non-clinical and clinical visits. CONCLUSION: Current Zambian ART clinic operations include substantial inefficiencies for both patients and HCWs, with workloads heavily concentrated in the first few hours of clinic opening, limiting HCW and patient interaction time. Use of a differentiated care model may help to redistribute workloads during operational hours and prevent backlogs of patients waiting for hours before clinic opening, which may substantially improve ART delivery in the Zambian context.Item Retention and viral suppression in a cohort of HIV patients on antiretroviral therapy in Zambia: Regionally representative estimates using a multistage-sampling-based approach.(2019-May) Sikazwe, Izukanji; Eshun-Wilson, Ingrid; Sikombe, Kombatende; Czaicki, Nancy; Somwe, Paul; Mody, Aaloke; Simbeza, Sandra; Glidden, David V.; Chizema, Elizabeth; Mulenga, Lloyd B.; Padian, Nancy; Duncombe, Chris J.; Bolton-Moore, Carolyn; Beres, Laura K.; Holmes, Charles B.; Geng, ElvinBACKGROUND: Although the success of HIV treatment programs depends on retention and viral suppression, routine program monitoring of these outcomes may be incomplete. We used data from the national electronic medical record (EMR) system in Zambia to enumerate a large and regionally representative cohort of patients on treatment. We traced a random sample with unknown outcomes (lost to follow-up) to document true care status and HIV RNA levels. METHODS AND FINDINGS: On 31 July 2015, we selected facilities from 4 provinces in 12 joint strata defined by facility type and province with probability proportional to size. In each facility, we enumerated adults with at least 1 clinical encounter after treatment initiation in the previous 24 months. From this cohort, we identified lost-to-follow-up patients (defined as 90 or more days late for their last appointment), selected a random sample, and intensively reviewed their records and traced them via phone calls and in-person visits in the community. In 1 of 4 provinces, we also collected dried blood spots (DBSs) for plasma HIV RNA testing. We used inverse probability weights to incorporate sampling outcomes into Aalen-Johansen and Cox proportional hazards regression to estimate retention and viremia. We used a bias analysis approach to correct for the known inaccuracy of plasma HIV RNA levels obtained from DBSs. From a total of 64 facilities with 165,464 adults on ART, we selected 32 facilities with 104,966 patients, of whom 17,602 (17%) were lost to follow-up: Those lost to follow-up had median age 36 years, 60% were female (N = 11,241), they had median enrollment CD4 count of 220 cells/μl, and 38% had WHO stage 1 clinical disease (N = 10,690). We traced 2,892 (16%) and found updated outcomes for 2,163 (75%): 412 (19%) had died, 836 (39%) were alive and in care at their original clinic, 457 (21%) had transferred to a new clinic, 255 (12%) were alive and out of care, and 203 (9%) were alive but we were unable to determine care status. Estimates using data from the EMR only suggested that 42.7% (95% CI 38.0%-47.1%) of new ART starters and 72.3% (95% CI 71.8%-73.0%) of all ART users were retained at 2 years. After incorporating updated data through tracing, we found that 77.3% (95% CI 70.5%-84.0%) of new initiates and 91.2% (95% CI 90.5%-91.8%) of all ART users were retained (at original clinic or transferred), indicating that routine program data underestimated retention in care markedly. In Lusaka Province, HIV RNA levels greater than or equal to 1,000 copies/ml were present in 18.1% (95% CI 14.0%-22.3%) of patients in care, 71.3% (95% CI 58.2%-84.4%) of lost patients, and 24.7% (95% CI 21.0%-29.3%). The main study limitations were imperfect response rates and the use of self-reported care status. CONCLUSIONS: In this region of Zambia, routine program data underestimated retention, and the point prevalence of unsuppressed HIV RNA was high when lost patients were accounted for. Viremia was prevalent among patients who unofficially transferred: Sustained engagement remains a challenge among HIV patients in Zambia, and targeted sampling is an effective strategy to identify such gaps in the care cascade and monitor programmatic progress.Item Accurate dried blood spots collection in the community using non-medically trained personnel could support scaling up routine viral load testing in resource limited settings.(2019) Sikombe, Kombatende; Hantuba, Cardinal; Musukuma, Kalo; Sharma, Anjali; Padian, Nancy; Holmes, Charles; Czaicki, Nancy; Simbeza, Sandra; Somwe, Paul; Bolton-Moore, Carolyn; Sikazwe, Izukanji; Geng, ElvinRegular plasma HIV-RNA testing for persons living with HIV on antiretroviral therapy (ART) is now the global standard, but as many as 60% of persons in Africa today on ART do not have access to standard laboratory HIV-RNA assays. As a result, patients in Zambia often receive treatment without any means of determining true virologic failure, which poses a risk of premature switch of ART regimens and widespread HIV drug resistance. Dry blood spots (DBS) on the other hand require unskilled personnel and less complex storage supply chain so are ideal to capture viral-load results from HIV patients outside clinic settings. We assess collection of DBS in the community using non-medically trained personnel (NMP) and documented challenges. We trained 23 NMP to collect DBS from lost to follow-up (LTFU) patients in 4 rural and urban Zambian districts. We developed a phlebotomy box to transport DBS without contamination at ambient temperature and concomitant training and standard operating procedures. We evaluated this through field observations, bi-weekly meetings, reports, and staff meetings. The laboratory assessed DBS quality for testing validity. We attempted to collect DBS from 357 participants in the community. Though individual reasons for refusal from the remaining 37% were not collected, NMPs reported privacy concerns, awkward box-size which drew attention in the community and fears of undisclosed uses of samples related to witchcraft and circulating narratives about past research. Successful DBS collection was not associated with patient gender, age, time on ART, enrolment CD4, facility. DBS viral-load collection by NMP is feasible in Zambia. Our training approach and assessments of NMP not part of the health system can be extended to patients by giving them more responsibility to manage their own differentiated care groups. Concerted efforts that compare collection of DBS by NMP to those collected by skilled-medical personnel are needed.Item Patients' Satisfaction with HIV Care Providers in Public Health Facilities in Lusaka: A Study of Patients who were Lost-to-Follow-Up from HIV Care and Treatment.(2020-Apr) Mukamba, Njekwa; Chilyabanyama, Obvious N.; Beres, Laura K.; Simbeza, Sandra; Sikombe, Kombatende; Padian, Nancy; Holmes, Charles; Sikazwe, Izukanji; Geng, Elvin; Schwartz, Sheree R.Prognosis among those who are HIV infected has improved but long-term retention is challenging. Health systems may benefit from routinely measuring patient satisfaction which is a potential driver of engagement in HIV care, but it is not often measured in Africa, and Zambia in particular. This study aims to internally validate a patient satisfaction tool, assess satisfaction among patients previously lost-to-follow up (LTFU) from HIV care in Lusaka province and to measure association between patient satisfaction with their original clinic and re-engagement in HIV care. A cross-sectional assessment of satisfaction was conducted by tracing sampled patients drawn from public health facilities. Our findings suggest that satisfaction tool, previously validated in USA, exhibits high internal consistency for measuring patient satisfaction in the Zambian health system. Patient satisfaction with healthcare providers is associated with re-engagement in HIV care. Future interventions on patient-centred care are likely to optimize and support retention in care.Item Understanding Engagement in HIV Programmes: How Health Services Can Adapt to Ensure No One Is Left Behind.(2020-Oct) Grimsrud, Anna; Wilkinson, Lynne; Eshun-Wilson, Ingrid; Holmes, Charles; Sikazwe, Izukanji; Katz, Ingrid T.PURPOSE OF REVIEW: Despite the significant progress in the HIV response, gaps remain in ensuring engagement in care to support life-long medication adherence and viral suppression. This review sought to describe the different points in the HIV care cascade where people living with HIV were not engaging and highlight promising interventions. RECENT FINDINGS: There are opportunities to improve engagement both between testing and treatment and to support re-engagement in care for those in a treatment interruption. The gap between testing and treatment includes people who know their HIV status and people who do not know their status. People in a treatment interruption include those who interrupt immediately following initiation, early on in their treatment (first 6 months) and late (after 6 months or more on ART). For each of these groups, specific interventions are required to support improved engagement. There are diverse needs and specific populations of people living with HIV who are not engaged in care, and differentiated service delivery interventions are required to meet their needs and expectations. For the HIV response to realise the 2030 targets, engagement will need to be supported by quality care and patient choice combined with empowered patients who are treatment literate and have been supported to improve self-management.
