Browsing by Author "Sikombe K"

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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 K; Hantuba C; Musukuma K; Sharma A; Padian N; Holmes C; Czaicki N; Simbeza S; Somwe P; Bolton-Moore C; Sikazwe I; Geng E; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, California, United States of America.; Division of Epidemiology, University of California, Berkeley, Berkeley, California, United States of America.; Center for Global Health and Quality, Georgetown University, Washington, District of Columbia, United States of America.; Division of Infectious Diseases, University of Alabama, Birmingham, Alabama, United States of America.; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Regular 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.
Characterizing the double-sided cascade of care for adolescents living with HIV transitioning to adulthood across Southern Africa.
(2020-Jan) Tsondai PR; Sohn AH; Phiri S; Sikombe K; Sawry S; Chimbetete C; Fatti G; Hobbins MA; Technau KG; Rabie H; Bernheimer J; Fox MP; Judd A; Collins IJ; Davies MA; Newlands Clinic, Harare, Zimbabwe.; Lighthouse Trust Clinic, Lilongwe, Malawi.; Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; MRC Clinical Trials Unit at UCL, University College London (UCL), London, United Kingdom.; Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand.; SolidarMed, Luzern, Switzerland.; Department of Paediatrics and Child Health, Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch, South Africa.; Harriet Shezi Children's Clinic, Wits Reproductive Health and HIV Research Unit, University of Witwatersrand, Johannesburg, South Africa.; Médecins Sans Frontiers, Khayelitsha, South Africa.; Kheth'Impilo, Cape Town, South Africa.; Department of Global Health and Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.; Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: As adolescents and young people living with HIV (AYLH) age, they face a "transition cascade," a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high-income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub-Saharan Africa, paediatric HIV care is mostly provided in decentralized, non-specialist primary care clinics, where "transition" may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when "transition" to autonomy might occur, we evaluated pre- and post-transition outcomes among AYLH. METHODS: We included AYLH aged <16 years at enrolment, receiving antiretroviral therapy (ART) within International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) sites (2004 to 2017) with no history of transferring care. Using the ages of 16, 18, 20 and 22 years as proxies for "transition to autonomy," we compared the outcomes: no gap in care (≥2 clinic visits) and viral suppression (HIV-RNA <400 copies/mL) in the 12 months before and after each age threshold. Using log-binomial regression, we examined factors associated with no gap in care (retention) in the 12 months post-transition. RESULTS: A total of 5516 AYLH from 16 sites were included at "transition" age 16 (transition-16y), 3864 at 18 (transition-18y), 1463 at 20 (transition-20y) and 440 at 22 years (transition-22y). At transition-18y, in the 12 months pre- and post-transition, 83% versus 74% of AYLH had no gap in care (difference 9.3 (95% confidence interval (CI) 7.8 to 10.9)); while 65% versus 62% were virally suppressed (difference 2.7 (-1.0 to 6.5%)). The strongest predictor of being retained post-transition was having no gap in the preceding year, across all transition age thresholds (transition-16y: adjusted risk ratio (aRR) 1.72; 95% CI (1.60 to 1.86); transition-18y: aRR 1.76 (1.61 to 1.92); transition-20y: aRR 1.75 (1.53 to 2.01); transition-22y: aRR 1.47; (1.21 to 1.78)). CONCLUSIONS: AYLH with gaps in care need targeted support to prevent non-retention as they take on greater responsibility for their healthcare. Interventions to increase virologic suppression rates are necessary for all AYLH ageing to adulthood.
Comparison of patient exit interviews with unannounced standardised patients for assessing HIV service delivery in Zambia: a study nested within a cluster randomised trial.
(2023-Jul-05) Sikombe K; Pry JM; Mody A; Rice B; Bukankala C; Eshun-Wilson I; Mutale J; Simbeza S; Beres LK; Mukamba N; Mukumbwa-Mwenechanya M; Mwamba D; Sharma A; Wringe A; Hargreaves J; Bolton-Moore C; Holmes C; Sikazwe IT; Geng E; Center for Innovation in Global Health, Georgetown University Medical Center, Washington, District of Columbia, USA.; Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.; Implementation Science Unit, Center for Infectious Disease Research in Zambia, Lusaka, Zambia kombatende.sikombe@cidrz.org.; Implementation Science Unit, Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Social and Behavioural Science Research Group, Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.; Internal Medicine, Washington University in St Louis School of Medicine, St Louis, Missouri, USA.; Department of Public Health, Environments and Society, London School of Hygiene and Tropical Medicine Faculty of Public Health and Policy, London, UK.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To compare unannounced standardised patient approach (eg, mystery clients) with typical exit interviews for assessing patient experiences in HIV care (eg, unfriendly providers, long waiting times). We hypothesise standardised patients would report more negative experiences than typical exit interviews affected by social desirability bias. SETTING: Cross-sectional surveys in 16 government-operated HIV primary care clinics in Lusaka, Zambia providing antiretroviral therapy (ART). PARTICIPANTS: 3526 participants aged ≥18 years receiving ART participated in the exit surveys between August 2019 and November 2021. INTERVENTION: Systematic sample (every n OUTCOME MEASURES: We compared patient experience among patients who received brief training prior to their care visit (explaining each patient experience construct in the exit survey, being anonymous, without manipulating behaviour) with those who did not undergo training on the survey prior to their visit. RESULTS: Among 3526 participants who participated in exit surveys, 2415 were untrained (56% female, median age 40 (IQR: 32-47)) and 1111 were trained (50% female, median age 37 (IQR: 31-45)). Compared with untrained, trained patients were more likely to report a negative care experience overall (adjusted prevalence ratio (aPR) for aggregate sum score: 1.64 (95% CI: 1.39 to 1.94)), with a greater proportion reporting feeling unwelcome by providers (aPR: 1.71 (95% CI: 1.20 to 2.44)) and witnessing providers behaving rude (aPR: 2.28 (95% CI: 1.63 to 3.19)). CONCLUSION: Trained patients were more likely to identify suboptimal care. They may have understood the items solicited better or felt empowered to be more critical. We trained existing patients, unlike studies that use 'standardised patients' drawn from outside the patient population. This low-cost strategy could improve patient-centred service delivery elsewhere. TRIAL REGISTRATION NUMBER: Assessment was nested within a parent study; www.pactr.org registered the parent study (PACTR202101847907585).
Cross-sectional study to assess depression among healthcare workers in Lusaka, Zambia during the COVID-19 pandemic.
(2023-Apr-05) Simbeza S; Mutale J; Mulabe M; Jere L; Bukankala C; Sikombe K; Sikazwe I; Bolton-Moore C; Mody A; Geng EH; Sharma A; Beres LK; Pry JM; Research Department, Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, Washington University in St Louis, St Louis, Missouri, USA.; Division of Infectious Diseases, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.; Implementation Science Unit, Research Department, Center for Infectious Disease Research in Zambia, Lusaka, Zambia.; Public Health Sciences, University of California Davis School of Medicine, Sacramento, California, USA.; Implementation Science Unit, Research Department, Center for Infectious Disease Research in Zambia, Lusaka, Zambia jmpry@ucdavis.edu.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: We sought to assess depression among healthcare workers (HCWs) in the context of COVID-19 in Lusaka Province, Zambia. DESIGN: This cross-sectional study is nested within a larger study, the Person-Centred Public Health for HIV Treatment in Zambia (PCPH), a cluster-randomised trial to assess HIV care and outcomes. SETTING: The research was conducted in 24 government-run health facilities from 11 August to 15 October 2020 during the first wave of the COVID-19 pandemic in Lusaka, Zambia. PARTICIPANTS: We used convenience sampling to recruit HCW participants who were previously enrolled in the PCPH study, had more than 6 months' experience working at the facility and were voluntarily willing to participate. PRIMARY OUTCOME MEASURES: We implemented the well-validated 9-question Patient Health Questionnaire (PHQ-9) to assess HCW depression. We used mixed-effects, adjusted Poisson regression to estimate the marginal probability of HCWs experiencing depression that may warrant intervention (PHQ-9 score ≥5) by healthcare facility. RESULTS: We collected PHQ-9 survey responses from 713 professional and lay HCWs. Overall, 334 (46.8%, 95% CI 43.1%, 50.6%) HCWs recorded a PHQ-9 score ≥5, indicating the need for further assessment and potential intervention for depression. We identified significant heterogeneity across facilities and observed a greater proportion of HCWs with symptoms of depression in facilities providing COVID-19 testing and treatment services. CONCLUSIONS: Depression may be a concern for a large proportion of HCWs in Zambia. Further work to understand the magnitude and aetiologies of depression among HCWs in the public sector is needed to design effective prevention and treatment interventions to meet the needs for mental health support and to minimise poor health outcomes.
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 K; Mody A; Goss CW; Simbeza S; Beres LK; Pry JM; Eshun-Wilson I; Sharma A; Mukamba N; Mulenga LB; Rice B; Mutale J; Zulu Dube A; Mulabe M; Hargreaves J; Bolton Moore C; Holmes CB; Sikazwe I; Geng EH; Johnson & Johnson, Cape Town, South Africa.; Department of Medicine, Georgetown University, Washington, DC, USA.; Implementation Science Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Public Health Sciences, School of Medicine, University of California, Davis, CA, USA.; Zambian Ministry of Health, Lusaka, Zambia.; Implementation Science Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Public Health Environments and Society, Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: kombatende.sikombe@cidrz.org.; Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA.; Implementation Science Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Division of Infectious Diseases, University of Alabama, Birmingham, AL, USA.; Department of Public Health Environments and Society, Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK; Sheffield Centre for Health and Related Research (SCHARR), School of Medicine and Population Health, University of Sheffield, Sheffield, UK.; Department of Public Health Environments and Society, Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK.; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.; Implementation Science Unit, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Effects of implementing universal and rapid HIV treatment on initiation of antiretroviral therapy and retention in care in Zambia: a natural experiment using regression discontinuity.
(2021-Dec) Mody A; Sikazwe I; Namwase AS; Wa Mwanza M; Savory T; Mwila A; Mulenga L; Herce ME; Mweebo K; Somwe P; Eshun-Wilson I; Sikombe K; Beres LK; Pry J; Holmes CB; Bolton-Moore C; Geng EH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Public Health Environments and Society, Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK.; Department of Medicine, Georgetown University, Washington, DC, USA.; Zambian Ministry of Health, Lusaka, Zambia.; Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA.; Center for Disease Control, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Division of Infectious Diseases, University of Alabama, Birmingham, AL, USA.; Division of Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA. Electronic address: aaloke.mody@wustl.edu.; Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Universal testing and treatment (UTT) for all people living with HIV has only been assessed under experimental conditions in cluster-randomised trials. The public health effectiveness of UTT policies on the HIV care cascade under real-world conditions is not known. We assessed the real-world effectiveness of universal HIV treatment policies that were implemented in Zambia on Jan 1, 2017. METHODS: We used data from Zambia's routine electronic health record system to analyse antiretroviral therapy (ART)-naive adults who newly enrolled in HIV care up to 1 year before and after the implementation of universal treatment (ie, Jan 1, 2016, to Jan 1, 2018) at 117 clinics supported by the Centre for Infectious Disease Research in Zambia. We used a regression discontinuity design to estimate the effects of implementing UTT on same-day ART initiation, ART initiation within 1 month, and retention on ART at 12 months (defined as clinic attendance 9-15 months after enrolment and at least 6 months on ART), under the assumption that patients presenting immediately before and after UTT implementation were balanced on both measured and unmeasured characteristics. We did an instrumental variable analysis to estimate the effect of same-day ART initiation under routine conditions on 12-month retention on ART. FINDINGS: 65 673 newly enrolled patients with HIV (40 858 [62·2%] female, median age 32 years [IQR 26-39], median CD4 count 287 cells per μL [IQR 147-466]) were eligible for inclusion in the analyses; 31 145 enrolled before implementation of UTT, and 34 528 enrolled after UTT. Implementation of universal treatment increased same-day ART initiation from 41·7% to 74·8% (risk difference [RD] 33·1%, 95% CI 30·5-35·7), ART initiation by 1 month from 69·6% to 87·0% (RD 17·4%, 15·5-19·3), and 12-month retention on ART from 56·2% to 63·3% (RD 7·1%, 4·3-9·9). ART initiation rates became more uniform across patient subgroups after implementation of universal treatment, but heterogeneity in 12-month retention on ART between subgroups was unchanged. Instrumental variable analyses indicated that same-day ART initiation in routine settings led to a 15·8% increase (95% CI 12·1-19·5) in 12-month retention on ART. INTERPRETATION: UTT policies implemented in Zambia increased the rapidity and uptake of ART, as well as retention on ART at 12 months, although overall retention on ART remained suboptimal. UTT policies reduced disparities in treatment initiation, but not 12-month retention on ART. Natural experiments reveal both the anticipated and unanticipated effects of real-world implementation and indicate the need for new strategies leveraging the short-term effects of UTT to cultivate long-term treatment success. FUNDING: National Institutes of Health.
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 CB; Sikazwe I; Sikombe K; Eshun-Wilson I; Czaicki N; Beres LK; Mukamba N; Simbeza S; Bolton Moore C; Hantuba C; Mwaba P; Phiri C; Padian N; Glidden DV; Geng E; University of California, San Francisco, San Francisco, California, United States of America.; Lusaka Apex Medical University, Lusaka, Zambia.; University of California, Berkeley, Berkeley, California, United States of America.; Stellenbosch University, Cape Town, South Africa.; Ministry of Health, Government of the Republic of Zambia, Lusaka, Zambia.; Georgetown University, Washington, DC, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; Johns Hopkins University, Baltimore, Maryland, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: 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.
Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia.
(2018-Jun) Mody A; Sikazwe I; Czaicki NL; Wa Mwanza M; Savory T; Sikombe K; Beres LK; Somwe P; Roy M; Pry JM; Padian N; Bolton-Moore C; Holmes CB; Geng EH; Department of Public Health, University of California, Davis, Davis, California, United States of America.; Division of Epidemiology, University of California, Berkeley, Berkeley, California, United States of America.; Department of International Health, Johns Hopkins University School of Public Health, Baltimore, Maryland, United States of America.; Division of HIV, ID and Global Medicine, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, California, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, University of Alabama, Birmingham, Alabama, United States of America.; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Although randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out sicker patients owing to increased patient volume). Using a regression discontinuity design, we sought to assess the effects of a previous change to Zambia's HIV treatment guidelines increasing the threshold for treatment eligibility from 350 to 500 cells/μL to anticipate effects of current global efforts to treat all PLWHs. METHODS AND FINDINGS: We analyzed antiretroviral therapy (ART)-naïve adults who newly enrolled in HIV care in a network of 64 clinics operated by the Zambian Ministry of Health and supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). Patients were restricted to those enrolling in a narrow window around the April 1, 2014 change to Zambian HIV treatment guidelines that raised the CD4 threshold for treatment from 350 to 500 cells/μL (i.e., August 1, 2013, to November 1, 2014). Clinical and sociodemographic data were obtained from an electronic medical record system used in routine care. We used a regression discontinuity design to estimate the effects of this change in treatment eligibility on ART initiation within 3 months of enrollment, retention in care at 6 months (defined as clinic attendance between 3 and 9 months after enrollment), and a composite of both ART initiation by 3 months and retention in care at 6 months in all new enrollees. We also performed an instrumental variable (IV) analysis to quantify the effect of actually initiating ART because of this guideline change on retention. Overall, 34,857 ART-naïve patients (39.1% male, median age 34 years [IQR 28-41], median CD4 268 cells/μL [IQR 134-430]) newly enrolled in HIV care during this period; 23,036 were analyzed after excluding patients around the threshold to allow for clinic-to-clinic variations in actual guideline uptake. In all newly enrolling patients, expanding the CD4 threshold for treatment from 350 to 500 cells/μL was associated with a 13.6% absolute increase in ART initiation within 3 months of enrollment (95% CI, 11.1%-16.2%), a 4.1% absolute increase in retention at 6 months (95% CI, 1.6%-6.7%), and a 10.8% absolute increase in the percentage of patients who initiated ART by 3 months and were retained at six months (95% CI, 8.1%-13.5%). These effects were greatest in patients who would have become newly eligible for ART with the change in guidelines: a 43.7% increase in ART initiation by 3 months (95% CI, 37.5%-49.9%), 13.6% increase in retention at six months (95% CI, 7.3%-20.0%), and a 35.5% increase in the percentage of patients on ART at 3 months and still in care at 6 months [95% CI, 29.2%-41.9%). We did not observe decreases in ART initiation or retention in patients not directly targeted by the guideline change. An IV analysis found that initiating ART in response to the guideline change led to a 37.9% (95% CI, 28.8%-46.9%) absolute increase in retention in care. Limitations of this study include uncertain generalizability under newer models of care, lack of laboratory data (e.g., viral load), inability to account for earlier stages in the HIV care cascade (e.g., HIV testing and linkage), and potential for misclassification of eligibility status or outcome. CONCLUSIONS: In this study, guidelines raising the CD4 threshold for treatment from 350 to 500 cells/μL were associated with a rapid rise in ART initiation as well as enhanced retention among newly treatment-eligible patients, without negatively impacting patients with lower CD4 levels. These data suggest that health systems in Zambia and other high-prevalence settings could substantially enhance engagement even among those with high CD4 levels (i.e., above 500 cells/μL) by expanding treatment without undermining existing care standards.
HIV care experiences and health priorities during the first wave of COVID-19: clients' perspectives - a qualitative study in Lusaka, Zambia.
(2022-Nov-30) Mukamba N; Sharma A; Mwamba C; Nyirenda H; Foloko M; Lumbo K; Christopoulos K; Simbeza S; Sikombe K; Holmes CB; Geng EH; Sikazwe I; Bolton-Moore C; Beres LK; London School of Hygiene and Tropical Medicine, London, UK.; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.; Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.; Centre for Global Health and Quality, Georgetown University Medical Center, Washington, DC, USA.; Division of Social and Behavioural Interventions, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Department of Research, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Research, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. Njekwa.Mukamba@cidrz.org.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The novel COVID-19 pandemic threatened to disrupt access to human immunodeficiency (HIV) treatment for persons living with HIV (PLHIV), two-thirds of whom live in sub-Saharan Africa. To inform a health system response supportive of continuity of care, we sought to understand clients' HIV care experiences and health priorities during the first wave of COVID-19 outbreak in Lusaka, Zambia. METHODS: Leveraging a study cohort of those who completed periodic SMS surveys on HIV care, we purposefully sampled 25 PLHIV after first confirmed COVID-19 case was reported in Zambia on 18 RESULTS: All participants were aware of COVID-19, and HIV care experiences and health priorities of clients were affected by associated changes at health system, household, and individual level. The health system instituted early clinic visits to provide 6-months of antiretroviral therapy (ART) for stable patients and 3-months for unstable patients to reduce clinic visits and wait times. Most patients welcomed this long-desired extended appointment spacing. Some reported feeling respected and engaged when health care workers telephoned requesting their early clinic visit. However, others felt discouraged by an absence of physical distancing during their clinic visit due to 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2) infection concerns. Several expressed a lack of clarity regarding next viral load monitoring date and means for receiving results. Patients suggested regular patient-facility communication by telephone and SMS. Patients emphasized that COVID-19 restrictions led to loss of employment and household income, exacerbating poverty and difficulties in taking ART. At individual level, most participants felt motivated to stay healthy during COVID-19 by ART adherence and regular laboratory monitoring. CONCLUSIONS: Clients' HIV care and health priorities during the first wave of COVID-19 in Lusaka province were varied with a combination of positive and negative experiences that occurred especially at health system and individual levels, while at household level, the experiences were all negative. More research is needed to understand how patients practice resiliency in the widespread context of socio-economic instability. Governments and patients must work together to find local, health systems solutions to support ART adherence and monitoring. Additionally, the health system should consider how to build on changes for long-term HIV management and service delivery.
How might improved estimates of HIV programme outcomes influence practice? A formative study of evidence, dissemination and response.
(2020-Oct-16) Mukamba N; Beres LK; Mwamba C; Law JW; Topp SM; Simbeza S; Sikombe K; Padian N; Holmes CB; Geng EH; Sikazwe I; Centre for Global Health and Quality, Georgetown University Medical Center, Washington, DC, United States of America.; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. njekwa.mukamba@gmail.com.; Division of Epidemiology, University of California, Berkeley, Berkeley, CA, United States of America.; Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, United States of America.; College of Public Health, Medicine and Veterinary Sciences, James Cook University, Townsville, Australia.; Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, San Francisco, CA, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: While HIV programmes have started millions of persons on life-saving antiretroviral therapy in Africa, longitudinal health information systems are frail and, therefore, data about long-term survival is often inaccurate or unknown to HIV programmes. The 'Better Information for Health in Zambia' (BetterInfo) Study - a regional sampling-based survey to assess retention and mortality in HIV programmes in Zambia - found both retention and mortality to be higher than prevailing estimates from national surveillance systems. We sought to understand how Zambian health decision-makers at different health system levels would respond to these new data, with a view to informing research translation. METHODS: We interviewed 25 purposefully sampled health decision-makers from community, facility, district, provincial and national levels. During the interviews, we shared retention and mortality estimates from both routine programme surveillance and those generated by the study. Transcripts were analysed for inductive and deductive themes, the latter drawing on Weiss's framework that policy-makers interpret and apply evidence as 'warning', 'guidance', 'reconceptualisation' or 'mobilisation of support'. FINDINGS: All decision-makers found study findings relevant and important. Decision-makers viewed the underestimates of mortality to be a warning about the veracity and informativeness of routine data systems. Decision-makers felt guided by the findings to improve data monitoring and, acknowledging limitations of routine data, utilised episodic patient tracing to support improved data accuracy. Findings catalysed renewed motivation and mobilisation by national level decision-makers for differentiated models of HIV care to improve patient outcomes and also improved data management systems to better capture patient outcomes. Inductive analysis highlighted a programmatic application data interpretation, in which study findings can influence facility and patient-level decision-making, quality of care and routine data management. CONCLUSIONS: New epidemiological data on patient outcomes were widely seen as informative and relevant and can potentially catalyse health system action such as using evaluations to supplement electronic medical record data to improve HIV programmes. Formative evidence suggests that targeting research dissemination at different levels of the health system will elicit different responses. Researchers supporting the translation of evidence to action should leverage all relevant levels of the health system to facilitate both policy and programmatic action.
Human-Centered Design Lessons for Implementation Science: Improving the Implementation of a Patient-Centered Care Intervention.
(2019-Dec) Beres LK; Simbeza S; Holmes CB; Mwamba C; Mukamba N; Sharma A; Munamunungu V; Mwachande M; Sikombe K; Bolton Moore C; Mody A; Koyuncu A; Christopoulos K; Jere L; Pry J; Ehrenkranz PD; Budden A; Geng E; Sikazwe I; Georgetown University, Washington, DC.; Department of Interna6onal Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.; University of California San Francisco, San Francisco, CA.; D'EVA Consulting, Washington, DC.; The Bill & Melinda Gates Foundation, Seattle, WA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Evidence-based HIV interventions often fail to reach anticipated impact due to insufficient utilization in real-world health systems. Human-centered design (HCD) represents a novel approach in tailoring innovations to fit end-users, narrowing the gap between efficacious interventions and impact at scale. METHODS: We combined a narrative literature review of HCD in HIV programs with our experience using HCD to redesign an intervention promoting patient-centered care (PCC) practices among health care workers (HCW) in Zambia. We summarize the use and results of HCD in the global HIV response and share case study insights to advance conceptualization of HCD applications. RESULTS: The literature review identified 13 articles (representing 7 studies) on the use of HCD in HIV. All studies featured HCD hallmarks including empathy development, user-driven inquiry, ideation, and iterative refinement. HCD was applied to mHealth design, a management intervention and pre-exposure prophylaxis delivery. Our HCD application addressed a behavioral service delivery target: changing HCW patient-centered beliefs, attitudes, and practices. Through in-depth developer-user interaction, our HCD approach revealed specific HCW support for and resistance to PCC, suggesting intervention revisions to improve feasibility and acceptability and PCC considerations that could inform implementation in transferable settings. CONCLUSIONS: As both a research and implementation tool, HCD has potential to improve effective implementation of the HIV response, particularly for product development; new intervention introduction; and complex system interventions. Further research on HCD application strengths and limitations is needed. Those promoting PCC may improve implementation success by seeking out resonance and anticipating the challenges our HCD process identified.
'I need time to start antiretroviral therapy': understanding reasons for delayed ART initiation among people diagnosed with HIV in Lusaka, Zambia'.
(2022-Dec) Mwamba C; Beres LK; Topp SM; Mukamba N; Simbeza S; Sikombe K; Mody A; Geng E; Holmes CB; Kennedy CE; Sikazwe I; Denison JA; Bolton Moore C; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Georgetown University, Washington, DC, USA.; Washington University School of Medicine in St. Louis, MO, USA.; Department of Public Health Environments and Society, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, United Kingdom.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Australia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: Rapid antiretroviral therapy (ART) initiation can improve patient outcomes such as viral suppression and prevent new infections. However, not everyone who can start ART does so immediately. METHODS: We conducted a qualitative study to inform interventions supporting rapid initiation in the 'Test and Start' era. We purposively sampled 20 adult patients living with HIV and a previous gap in care from ten health facilities in Lusaka, Zambia for interviews. We inductively analysed transcripts using a thematic, narrative approach. In their narratives, seven participants discussed delaying ART initiation. RESULTS: Drawing on messages gleaned from facility-based counselling and community information, many cited greater fear of rapid sickness or death due to imperfect adherence or treatment side effects than negative health consequences due to delayed initiation. Participants described needing time to 'prepare' their minds for a lifetime treatment commitment. Concerns about inadvertent HIV status disclosure during drug collection discouraged immediate initiation, as did feeling healthy, and worries about the impact of ART initiation on relationship dynamics. CONCLUSION: Findings suggest that counselling messages should accurately communicate treatment risks, without perpetuating fear-based narratives about HIV. Identifying and managing patient-specific concerns and reasons for the 'need for time' may be important for supporting individuals to rapidly accept lifelong treatment.Key messagesFear-based adherence messaging in health facilities about the dangers of missing a treatment dose or changing the time when ART is taken contributes to Zambian patients' refusals of immediate ART initiationResponsive health systems that balance a stated need for time to accept one's diagnosis and prepare to embark on a lifelong treatment plan with interventions to identify and manage patient-specific treatment related fears and concerns may support more rapid ART initiationPerceived social stigma around HIV continues to be a significant challenge for treatment initiation.
Improved Retention With 6-Month Clinic Return Intervals for Stable Human Immunodeficiency Virus-Infected Patients in Zambia.
(2018-Jan-06) Mody A; Roy M; Sikombe K; Savory T; Holmes C; Bolton-Moore C; Padian N; Sikazwe I; Geng E; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Division of HIV, ID, and Global Medicine, University of California, San Francisco and Zuckerberg San Francisco General Hospital.; Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.; Division of Infectious Diseases, University of Alabama, Birmingham.; Division of Epidemiology, University of California, Berkeley.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Extending appointment intervals for stable HIV-infected patients in sub-Saharan Africa can reduce patient opportunity costs and decongest overcrowded facilities. METHODS: We analyzed a cohort of stable HIV-infected adults (on treatment with CD4 >200 cells/μL for more than 6 months) who presented for clinic visits in Lusaka, Zambia. We used multilevel, mixed-effects logistic regression adjusting for patient characteristics, including prior retention, to assess the association between scheduled appointment intervals and subsequent missed visits (>14 days late to next visit), gaps in medication (>14 days late to next pharmacy refill), and loss to follow-up (LTFU; >90 days late to next visit). RESULTS: A total of 62084 patients (66.6% female, median age 38, median CD4 438 cells/μL) made 501281 visits while stable on antiretroviral therapy. Most visits were scheduled around 1-month (25.0% clinical, 44.4% pharmacy) or 3-month intervals (49.8% clinical, 35.2% pharmacy), with fewer patients scheduled at 6-month intervals (10.3% clinical, 0.4% pharmacy). After adjustment and compared to patients scheduled to return in 1 month, patients with six-month clinic return intervals were the least likely to miss visits (adjusted odds ratio [aOR], 0.20; 95% confidence interval [CI], 0.17-0.24); miss medication pickups (aOR, 0.47; 95% CI 0.39-0.57), and become LTFU prior to the next visit (aOR, 0.41; 95% CI, 0.31-0.54). CONCLUSIONS: Six-month clinic return intervals were associated with decreased lateness, gaps in medication, and LTFU in stable HIV-infected patients and may represent a promising strategy to reduce patient burdens and decongest clinics.
Intention to receive new vaccines post-COVID-19 pandemic among adults and health workers in Lusaka, Zambia.
(2025-Mar-19) Sharma A; Kerkhoff AD; Haambokoma M; Shamoya B; Sikombe K; Simbeza SS; Zulu N; Geng EH; Eshun-Wilsonova I; Le Tourneau N; Pry JM; Division of Infectious Diseases, School of Medicine, Washington University in St. Louis, Saint Louis, MO, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Division of Epidemiology, School of Medicine, University of California, Davis, California, United States of America. Electronic address: jmpry@ucdavis.edu.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Division of HIV, Infectious Diseases and Global Medicine Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, California, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVES: To estimate intention to receive newly introduced adult vaccines among community members and healthcare workers (HCWs) in Lusaka, Zambia in the context of previous COVID-19 vaccine uptake and perceived disease threat and, identify trusted sources of vaccine information. METHODS: We conducted a cross-sectional survey among a random sample of community members and a convenience sample of HCWs from 13 November to 15 December 2023. We evaluated future vaccination intentions by self-reported COVID-19 vaccine uptake, community role, vaccine type (COVID-19 booster, HIV, tuberculosis, malaria, pneumonia, diarrheal disease) and source of information using adjusted, mixed effects Poisson regression and adjusted probability models. RESULTS: We enrolled 395 (79.2 %) community members and 104 (20.8 %) HCWs (N = 499). There was high intention to receive new vaccines among community members (mean score = 83.6 %) and HCWs (mean score = 86.0 %), though intentions varied by vaccine type. Prior COVID-19 vaccine uptake (0, 1, 2+ doses) impacted intentions to receive a novel COVID-19 vaccine among community members (43.3 %, 62.8 %, 79.7 %, respectively) but were not associated with any other vaccine types. Intention to receive a vaccine was strongly associated with perceived disease severity and susceptibility as well as age, sex, education, and household income. Social media as a vaccine information source was associated with lower overall vaccine intention among community members, while health system and community sources were associated with higher overall intention to receive new vaccines. Government was a highly trusted source of vaccine information among all participants. CONCLUSION: Prior COVID-19 vaccination uptake did not predict future non-COVID-19 vaccine intention in Zambia. Perceived threat and select socio-demographic factors were key predictors, suggesting the need for rapid research to design communication strategies and identify trusted sources per target population.
Longitudinal Care Cascade Outcomes Among People Eligible for Antiretroviral Therapy Who Are Newly Linking to Care in Zambia: A Multistate Analysis.
(2020-Dec-17) Mody A; Glidden DV; Eshun-Wilson I; Sikombe K; Simbeza S; Mukamba N; Somwe P; Beres LK; Pry J; Bolton-Moore C; Padian N; Holmes CB; Sikazwe I; Geng EH; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, Washington University School of Medicine, St. Louis, Missouri, USA.; Division of Epidemiology, University of California, Berkeley, Berkeley, California, USA.; Division of Infectious Diseases, University of Alabama, Birmingham, Alabama, USA.; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.; Department of International Health, Johns Hopkins University School of Public Health, Baltimore, Maryland, USA.; Department of Medicine, Georgetown University, Washington, D.C., USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Retention in human immunodeficiency virus (HIV) care is dynamic, with patients frequently transitioning in and out of care. Analytical approaches (eg, survival analyses) commonly used to assess HIV care cascade outcomes fail to capture such transitions and therefore incompletely represent care outcomes over time. METHODS: We analyzed antiretroviral therapy (ART)-eligible adults newly linking to care at 64 clinics in Zambia between 1 April 2014 and 31 July 2015. We used electronic medical record data and supplemented these with updated care outcomes ascertained by tracing a multistage random sample of patients lost to follow-up (LTFU, >90 days late for last appointment). We performed multistate analyses, incorporating weights from sampling, to estimate the prevalence of 9 care states over time since linkage with respect to ART initiation, retention in care, transfers, and mortality. RESULTS: In sum, 23 227 patients (58% female; median age 34 years [interquartile range 28-41]) were ART-eligible at enrollment. At 1 year, 75.2% had initiated ART and were in care: 61.8% were continuously retained, 6.1% had reengaged after LTFU, and 7.3% had transferred. Also, 10.1% were LTFU within 7 days of enrollment, and 15.2% were LTFU at 1 year (6.7% prior to ART). One year after LTFU, 51.6% of those LTFU prior to ART remained out of care compared to 30.2% of those LTFU after initiating ART. Overall, 6.9% of patients had died by 1 year with 3.0% dying prior to ART. CONCLUSION: Multistate analyses provide more complete assessments of longitudinal HIV cascade outcomes and reveal treatment gaps at distinct timepoints in care that will still need to be addressed even with universal treatment.
Longitudinal engagement trajectories and risk of death among new ART starters in Zambia: A group-based multi-trajectory analysis.
(2019-Oct) Mody A; Eshun-Wilson I; Sikombe K; Schwartz SR; Beres LK; Simbeza S; Mukamba N; Somwe P; Bolton-Moore C; Padian N; Holmes CB; Sikazwe I; Geng EH; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.; Division of HIV, ID and Global Medicine, University of California, San Francisco, Zuckerberg San Francisco General Hospital, San Francisco, California, United States of America.; Division of Epidemiology, University of California, Berkeley, California, United States of America.; Department of Medicine, Georgetown University, Washington, District of Columbia, United States of America.; Division of Infectious Diseases, University of Alabama at Birmingham, Alabama, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Retention in HIV treatment must be improved to advance the HIV response, but research to characterize gaps in retention has focused on estimates from single time points and population-level averages. These approaches do not assess the engagement patterns of individual patients over time and fail to account for both their dynamic nature and the heterogeneity between patients. We apply group-based trajectory analysis-a special application of latent class analysis to longitudinal data-among new antiretroviral therapy (ART) starters in Zambia to identify groups defined by engagement patterns over time and to assess their association with mortality. METHODS AND FINDINGS: We analyzed a cohort of HIV-infected adults who newly started ART between August 1, 2013, and February 1, 2015, across 64 clinics in Zambia. We performed group-based multi-trajectory analysis to identify subgroups with distinct trajectories in medication possession ratio (MPR, a validated adherence metric based on pharmacy refill data) over the past 3 months and loss to follow-up (LTFU, >90 days late for last visit) among patients with at least 180 days of observation time. We used multinomial logistic regression to identify baseline factors associated with belonging to particular trajectory groups. We obtained Kaplan-Meier estimates with bootstrapped confidence intervals of the cumulative incidence of mortality stratified by trajectory group and performed adjusted Poisson regression to estimate adjusted incidence rate ratios (aIRRs) for mortality by trajectory group. Inverse probability weights were applied to all analyses to account for updated outcomes ascertained from tracing a random subset of patients lost to follow-up as of July 31, 2015. Overall, 38,879 patients (63.3% female, median age 35 years [IQR 29-41], median enrollment CD4 count 280 cells/μl [IQR 146-431]) were included in our cohort. Analyses revealed 6 trajectory groups among the new ART starters: (1) 28.5% of patients demonstrated consistently high adherence and retention; (2) 22.2% showed early nonadherence but consistent retention; (3) 21.6% showed gradually decreasing adherence and retention; (4) 8.6% showed early LTFU with later reengagement; (5) 8.7% had early LTFU without reengagement; and (6) 10.4% had late LTFU without reengagement. Identified groups exhibited large differences in survival: after adjustment, the "early LTFU with reengagement" group (aIRR 3.4 [95% CI 1.2-9.7], p = 0.019), the "early LTFU" group (aIRR 6.4 [95% CI 2.5-16.3], p < 0.001), and the "late LTFU" group (aIRR 4.7 [95% CI 2.0-11.3], p = 0.001) had higher rates of mortality as compared to the group with consistently high adherence/retention. Limitations of this study include using data observed after baseline to identify trajectory groups and to classify patients into these groups, excluding patients who died or transferred within the first 180 days, and the uncertain generalizability of the data to current care standards. CONCLUSIONS: Among new ART starters in Zambia, we observed 6 patient subgroups that demonstrated distinctive engagement trajectories over time and that were associated with marked differences in the subsequent risk of mortality. Further efforts to develop tailored intervention strategies for different types of engagement behaviors, monitor early engagement to identify higher-risk patients, and better understand the determinants of these heterogeneous behaviors can help improve care delivery and survival in this population.
Lost in translation: key lessons from conducting dissemination and implementation science in Zambia.
(2024-Oct-29) Maritim P; Munakampe MN; Nglazi M; Mweemba C; Sikombe K; Mbewe W; Silumbwe A; Jacobs C; Zulu JM; Herce M; Mutale W; Halwindi H; Department of Health Policy and Management, School of Public Health, University of Zambia, Lusaka, Zambia. triciamarie20@gmail.com.; Implementation Science Centre for Advancing Practice and Training (IMPACT), University of Zambia, Lusaka, Zambia. triciamarie20@gmail.com.; Implementation Science Centre for Advancing Practice and Training (IMPACT), University of Zambia, Lusaka, Zambia.; Department of Epidemiology and Biostatistics, School of Public Health, University of Zambia, Lusaka, Zambia.; Ministry of Health, Lusaka, Zambia.; Implementation Science Department, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Department of Health Policy and Management, School of Public Health, University of Zambia, Lusaka, Zambia.
BACKGROUND: As the field of implementation science continues to grow, its key concepts are being transferred into new contexts globally, such as Low and Middle Income Countries (LMICs), and its use is constantly being reexamined and expanded. Theoretical and methodological positions commonly used in implementation research and practice have great utility in our work but in many cases are at odds with LMIC contexts. As a team of implementation scientists based in Zambia, we offer this commentary as a critical self-reflection on what has worked and what could limit us from fully utilizing the field's promise for addressing health problems with contextual understanding. MAIN BODY: We used a 'premortem,' an approach used to generate potential alternatives from failed assumptions about a particular phenomenon, as a way to reflect on our experiences conducting implementation research and practice. By utilizing prospectively imagined hindsights, we were able to reflect on the past, present and possible future of the field in Zambia. Six key challenges identified were: (i) epistemic injustices; (ii) simplified conceptualizations of evidence-informed interventions; (iii) limited theorization of the complexity of low-resource contexts and it impacts on implementation; (iv) persistent lags in transforming research into practice; (v) limited focus on strategic dissemination of implementation science knowledge and (vi) existing training and capacity building initiatives' failure to engage a broad range of actors including practitioners through diverse learning models. CONCLUSION: Implementation science offers great promise in addressing many health problems in Zambia. Through this commentary, we hope to spur discussions on how implementation scientists can reimagine the future of the field by contemplating on lessons from our experiences in LMIC settings.
Mitigating the effects of COVID-19 on HIV treatment and care in Lusaka, Zambia: a before-after cohort study using mixed effects regression.
(2022-Jan) Pry JM; Sikombe K; Mody A; Iyer S; Mutale J; Vlahakis N; Savory T; Wa Mwanza M; Mweebo K; Mwila A; Mwale C; Mukumbwa-Mwenechanya M; Kerkhoff AD; Sikazwe I; Bolton Moore C; Mwamba D; Geng EH; Herce ME; Department of Infectious Disease, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA.; University of California San Francisco, San Francisco, California, USA.; San Francisco General Hospital and Trauma Center, San Francisco, California, USA.; Zambia Ministry of Health, Lusaka, Zambia.; Division of Global HIV & Tuberculosis, Centers for Disease Control and Prevention, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia jmpry@ucdavis.edu.; Institute for Global Health & Infectious Diseases, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.; Department of Public Health Environments and Society, London School of Hygiene & Tropical Medicine, London, UK.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Department of Internal Medicine, Washington University School of Medicine in Saint Louis, St Louis, Missouri, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation. METHODS: We reviewed all ART pharmacy visit data in the national HIV medical record for PLHIV in care having ≥1 visit between 1 January-30 June 2020 at 59 HIV care facilities in Lusaka Province, Zambia. We undertook a before-after evaluation using mixed-effects Poisson regression to examine predictors and marginal probability of early clinic return (pharmacy visit >7 days before next appointment), proportion of late visit (>7 days late for next appointment) and probability of receiving a 6MMD ART refill. RESULTS: A total of 101 371 individuals (64% female, median age 39) with 130 486 pharmacy visits were included in the analysis. We observed a significant increase in the adjusted prevalence ratio (4.63; 95% CI 4.45 to 4.82) of early return before compared with after guidance implementation. Receipt of 6MMD increased from a weekly mean of 47.9% (95% CI 46.6% to 49.2%) before to 73.4% (95% CI 72.0% to 74.9%) after guidance implementation. The proportion of late visits (8-89 days late) was significantly higher before (18.8%, 95% CI17.2%to20.2%) compared with after (15.1%, 95% CI13.8%to16.4%) guidance implementation . CONCLUSIONS: Timely issuance and implementation of COVID-19 mitigation guidance involving task-shifted patient communication and mobilisation alongside 6MMD significantly increased early return to ART clinic, potentially reducing interruptions in HIV care during a global public health emergency.
Mortality estimates by age and sex among persons living with HIV after ART initiation in Zambia using electronic medical records supplemented with tracing a sample of lost patients: A cohort study.
(2020-May) Kerkhoff AD; Sikombe K; Eshun-Wilson I; Sikazwe I; Glidden DV; Pry JM; Somwe P; Beres LK; Simbeza S; Mwamba C; Bukankala C; Hantuba C; Moore CB; Holmes CB; Padian N; Geng EH; Georgetown University, Washington, District of Columbia, United States of America.; Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California, San Francisco, San Francisco, California, United States of America.; University of California, Berkeley, Berkeley, California, United States of America.; Division of Infectious Diseases, Department of Medicine, Washington University, St. Louis, Missouri, United States of America.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; Johns Hopkins University, Baltimore, Maryland, United States of America.; Center for Dissemination and Implementation, Institute for Public Health, Washington University, St. Louis, Missouri, United States of America.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Men in sub-Saharan Africa have lower engagement and retention in HIV services compared to women, which may result in differential survival. However, the true magnitude of difference in HIV-related mortality between men and women receiving antiretroviral therapy (ART) is incompletely characterized. METHODS AND FINDINGS: We evaluated HIV-positive adults ≥18 years old newly initiating ART in 4 Zambian provinces (Eastern, Lusaka, Southern, and Western). In addition to mortality data obtained from routine electronic medical records, we intensively traced a random sample of patients lost to follow-up (LTFU) and incorporated tracing outcomes through inverse probability weights. Sex-specific mortality rates and rate differences were determined using Poisson regression. Parametric g-computation was used to estimate adjusted mortality rates by sex and age. The study included 49,129 adults newly initiated on ART between August 2013 and July 2015; overall, the median age among patients was 35 years, the median baseline CD4 count was 262 cells/μl, and 37.2% were men. Men comprised a smaller proportion of individuals starting ART (37.2% versus 62.8%), tended to be older (median age 37 versus 33 years), and tended to have lower CD4 counts (median 220 versus 289 cells/μl) at the time of ART initiation compared to women. The overall rate of mortality among men was 10.3 (95% CI 8.2-12.4) deaths/100 person-years (PYs), compared to 5.5 (95% CI 4.3-6.8) deaths/100 PYs among women (difference +4.7 [95% CI 2.3-7.2] deaths/100 PYs; p < 0.001). Compared to women in the same age groups, men's mortality rates were particularly elevated among those <30 years old (+6.7 deaths/100 PYs difference), those attending rural health centers (+9.4 deaths/100 PYs difference), those who had an initial CD4 count < 100 cells/μl (+9.2 deaths/100 PYs difference), and those who were unmarried (+8.0 deaths/100 PYs difference). After adjustment for potential confounders and mediators including CD4 count, a substantially higher mortality rate was predicted among men <30 years old compared to women of the same age, while women ≥50 years old had a mortality rate similar to that of age-matched men, but considerably higher than that predicted among young women (<30 years old). No clinically significant differences were evident with respect to rates of facility transfer or care disengagement between men and women. The main study limitations were the inability to successfully ascertain outcomes in all patients selected for tracing and missing clinical and laboratory data due to the use of medical records. CONCLUSIONS: In this study, we found that among HIV-positive adults newly initiating ART, mortality among men exceeded mortality among women; disparities were most pronounced among young patients. Older women, however, also experienced high mortality. Specific interventions for men and older women at highest mortality risk are needed to improve HIV treatment outcomes.
Novel Longitudinal Methods for Assessing Retention in Care: a Synthetic Review.
(2021-Aug) Mody A; Tram KH; Glidden DV; Eshun-Wilson I; Sikombe K; Mehrotra M; Pry JM; Geng EH; Centre for Infectious Diseases Research in Zambia, Lusaka, Zambia.; Division of Infectious Diseases, Washington University School of Medicine, Campus Box 8051, 4523 Clayton Avenue, St. Louis, Missouri, 63110, USA. aaloke.mody@wustl.edu.; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.; Division of Infectious Diseases, Washington University School of Medicine, Campus Box 8051, 4523 Clayton Avenue, St. Louis, Missouri, 63110, USA.; Department of Public Health Environments and Society, Faculty of Public Health and Policy, London School of Hygiene and Tropical Medicine, London, UK.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
PURPOSE OF REVIEW: Retention in care is both dynamic and longitudinal in nature, but current approaches to retention often reduce these complex histories into cross-sectional metrics that obscure the nuanced experiences of patients receiving HIV care. In this review, we discuss contemporary approaches to assessing retention in care that captures its dynamic nature and the methodological and data considerations to do so. RECENT FINDINGS: Enhancing retention measurements either through patient tracing or "big data" approaches (including probabilistic matching) to link databases from different sources can be used to assess longitudinal retention from the perspective of the patient when they transition in and out of care and access care at different facilities. Novel longitudinal analytic approaches such as multi-state and group-based trajectory analyses are designed specifically for assessing metrics that can change over time such as retention in care. Multi-state analyses capture the transitions individuals make in between different retention states over time and provide a comprehensive depiction of longitudinal population-level outcomes. Group-based trajectory analyses can identify patient subgroups that follow distinctive retention trajectories over time and highlight the heterogeneity of retention patterns across the population. Emerging approaches to longitudinally measure retention in care provide nuanced assessments that reveal unique insights into different care gaps at different time points over an individuals' treatment. These methods help meet the needs of the current scientific agenda for retention and reveal important opportunities for developing more tailored interventions that target the varied care challenges patients may face over the course of lifelong treatment.