Browsing by Author "Bolton Moore C"

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A controlled study to assess the effects of a Fast Track (FT) service delivery model among stable HIV patients in Lusaka Zambia.
(2022) Bolton Moore C; Pry JM; Mukumbwa-Mwenechanya M; Eshun-Wilson I; Topp S; Mwamba C; Roy M; Sohn H; Dowdy DW; Padian N; Holmes CB; Geng EH; Sikazwe I; Georgetown University, School of Medicine, Washington, DC, United States of America.; University of California, School of Medicine, San Francisco, California, United States of America.; University of California, School of Public Health, Berkeley, California, United States of America.; Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.; University of Alabama, School of Medicine, Birmingham, Alabama, United States of America.; James Cook University, College of Public Health, Medical and Vet Sciences, Queensland, Australia.; Washington University, School of Medicine, St Louis, Missouri, United States of America.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; University of California, School of Medicine, Davis, California, United States of America.
Fast Track models-in which patients coming to facility to pick up medications minimize waiting times through foregoing clinical review and collecting pre-packaged medications-present a potential strategy to reduce the burden of treatment. We examine effects of a Fast Track model (FT) in a real-world clinical HIV treatment program on retention to care comparing two clinics initiating FT care to five similar (in size and health care level), standard of care clinics in Zambia. Within each clinic, we selected a systematic sample of patients meeting FT eligibility to follow prospectively for retention using both electronic medical records as well as targeted chart review. We used a variety of methods including Kaplan Meier (KM) stratified by FT, to compare time to first late pick up, exploring late thresholds at >7, >14 and >28 days, Cox proportional hazards to describe associations between FT and late pick up, and linear mixed effects regression to assess the association of FT with medication possession ratio. A total of 905 participants were enrolled with a median age of 40 years (interquartile range [IQR]: 34-46 years), 67.1% were female, median CD4 count was 499 cells/mm3 (IQR: 354-691), and median time on ART was 5 years (IQR: 3-7). During the one-year follow-up period FT participants had a significantly reduced cumulative incidence of being >7 days late for ART pick-up (0.36, 95% confidence interval [CI]: 0.31-0.41) compared to control participants (0.66; 95% CI: 0.57-0.65). This trend held for >28 days late for ART pick-up appointments, at 23% (95% CI: 18%-28%) among intervention participants and 54% (95% CI: 47%-61%) among control participants. FT models significantly improved timely ART pick up among study participants. The apparent synergistic relationship between refill time and other elements of the FT suggest that FT may enhance the effects of extending visit spacing/multi-month scripting alone. ClinicalTrials.gov Identifier: NCT02776254 https://clinicaltrials.gov/ct2/show/NCT02776254.
A Review of Differentiated Service Delivery for HIV Treatment: Effectiveness, Mechanisms, Targeting, and Scale.
(2019-Aug) Roy M; Bolton Moore C; Sikazwe I; Holmes CB; Center for Global Health and Quality, Georgetown University School of Medicine, Washington, DC, USA.; Division of HIV, Infectious Diseases, and Global Medicine, San Francisco General Hospital, University of California, San Francisco, 995 Potrero Avenue, Bldg 80, San Francisco, CA, 94110, USA. monika.roy@ucsf.edu.; Johns Hopkins University School of Medicine, Baltimore, MD, USA.; University of Alabama, Birmingham, AL, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
PURPOSE OF REVIEW: Differentiated service delivery (DSD) models were initially developed as a means to combat suboptimal long-term retention in HIV care, and to better titrate limited health systems resources to patient needs, primarily in low-income countries. The models themselves are designed to streamline care along the HIV care cascade and range from individual to group-based care and facility to community-based health delivery systems. However, much remains to be understood about how well and for whom DSD models work and whether these models can be scaled, are sustainable, and can reach vulnerable and high-risk populations. Implementation science is tasked with addressing some of these questions through systematic, scientific inquiry. We review the available published evidence on the implementation of DSD and suggest further health systems innovations needed to maximize the public health impact of DSD and future implementation science research directions in this expanding field. RECENT FINDINGS: While early observational data supported the effectiveness of various DSD models, more recently published trials as well as evaluations of national scale-up provide more rigorous evidence for effectiveness and performance at scale. Deeper understanding of the mechanism of effect of various DSD models and generalizability of studies to other countries or contexts remains somewhat limited. Relative implementability of DSD models may differ based on patient preference, logistical complexity of model adoption and maintenance, human resource and pharmacy supply chain needs, and comparative cost-effectiveness. However, few studies to date have evaluated comparative implementation or cost-effectiveness from a health systems perspective. While DSD represents an exciting and promising "next step" in HIV health care delivery, this innovation comes with its own set of implementation challenges. Evidence on the effectiveness of DSD generally supports the use of most DSD models, although it is still unclear which models are most relevant in diverse settings and populations and which are the most cost-effective. Challenges during scale-up highlight the need for accurate differentiation of patients, sustainable inclusion of a new cadre of health care worker (the community health care worker), and substantial strengthening of existing pharmacy supply chains. To maximize the public health impact of DSD, systems need to be patient-centered and adaptive, as well as employ robust quality improvement processes.
Application of a Multistate Model to Evaluate Visit Burden and Patient Stability to Improve Sustainability of Human Immunodeficiency Virus Treatment in Zambia.
(2018-Sep-28) Roy M; Holmes C; Sikazwe I; Savory T; Mwanza MW; Bolton Moore C; Mulenga K; Czaicki N; Glidden DV; Padian N; Geng E; Division of Epidemiology, University of California Berkeley.; Division of HIV/AIDS, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco General Hospital.; Centre for Infectious Diseases Research in Zambia, Lusaka.; Department of Epidemiology and Biostatistics, University of California, San Francisco.; University of Alabama, Birmingham.; Johns Hopkins University School of Medicine, Baltimore, Maryland.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Differentiated service delivery (DSD) for human immunodeficiency virus (HIV)-infected persons who are clinically stable on antiretroviral therapy (ART) has been embraced as a solution to decrease access barriers and improve quality of care. However, successful DSD implementation is dependent on understanding the prevalence, incidence, and durability of clinical stability. METHODS: We evaluated visit data in a cohort of HIV-infected adults who made at least 1 visit between 1 March 2013 and 28 February 2015 at 56 clinics in Zambia. We described visit frequency and appointment intervals using conventional stability criteria and used a mixed-effects linear regression model to identify predictors of appointment interval. We developed a multistate model to characterize patient stability over time and calculated incidence rates for transition between states. RESULTS: Overall, 167819 patients made 3418018 post-ART initiation visits between 2004 and 2015. Fifty-four percent of visits were pharmacy refill-only visits, and 24% occurred among patients on ART for >6 months and whose current CD4 was >500 cells/mm3. Median appointment interval at clinician visits was 59 days, and time on ART and current CD4 were not strong predictors of appointment interval. Cumulative incidence of clinical stability was 66.2% at 2 years after enrollment, but transition to instability (31 events per 100 person-years) and lapses in care (41 events per100 person-years) were common. CONCLUSIONS: Current facility-based care was characterized by high visit burden due to pharmacy refills and among treatment-experienced patients. Differentiated service delivery models targeted toward stable patients need to be adaptive given that clinical stability was highly transient and lapses in care were common.
Barriers to HIV care and adherence for young people living with HIV in Zambia and mHealth.
(2019) St Clair-Sullivan N; Mwamba C; Whetham J; Bolton Moore C; Darking M; Vera J; Brighton and Sussex Medical School, Brighton, East Sussex, UK.; School of Applied Social Science, Brighton, UK.; Brighton and Sussex Medical School, Brighton, East Sussex UK.; University of Alabama at Birmingham, Birmingham, USA.; Brighton and Sussex University NHS Trust, Brighton, UK.; Centre for Infectious Disease Research in Zambia, Mass Media, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The control of HIV/AIDS has been a contemporary public health success story however, whilst infection rates are falling and people are living longer due to antiretroviral therapy, adolescents and young people remain disproportionally affected. Infection rates and AIDS-related deaths continue to increase in these age groups in some areas globally. This has been primarily attributed to structural barriers including HIV-services not being youth friendly with opening hours conflicting with school time, fears around unintended disclosure and confidentiality, and the attitudes of healthcare professionals-but research targeting these specific age groups remains limited. Early mHealth (i.e., the use of mobile and wireless devices to assist in achieving health objectives) projects have been shown to improve health outcomes in other disease areas and health settings however, amongst people living with HIV, current research is limited. The aim of this study was to explore barriers to HIV care and the acceptability and feasibility of using mHealth to improve retention into care and ART adherence for young people living with HIV (16-24 years old) in Lusaka, Zambia. METHODS: Qualitative in-depth interviews and focus group discussions were carried out in four CIDRZ-supported health facilities in Lusaka, Zambia. Six interviews were carried out with nurses and peer-support workers working with young people living with HIV and three focus groups with a total of 24 young people. Recruitment was via purposive sampling. Interviews and focus groups were recorded, translated and transcribed and entered into NVivo for thematic analysis. RESULTS: Twenty-four of the young persons interviewed had access to mobile phones and reported using them for social networking, information gathering and regular communication. Barriers to HIV care and adherence were largely underpinned by stigma. Participants described healthcare facilities as not being conducive for confidentiality and therefore were reluctant to be seen attending or collecting medication from the pharmacy due to possible unintended disclosure and consequential HIV-related stigma. Clinic opening and waiting times and experiences with healthcare professionals also served as barriers. It was felt unanimously by participants that mHealth would be beneficial in improving retention into care and ART adherence in young people living with HIV. CONCLUSIONS: HIV-related stigma remains a barrier to care. With growing access to mobile phones and internet, and a growing population of adolescents who are already using their phones to support each other and seek information, mHealth appears to be both a feasible and acceptable tool to support retention, provide young people with information, and potentially reduce time spent at health facilities via appointment reminders and electronic drug refill requests.
Cervical cancer screening outcomes in Zambia, 2010-19: a cohort study.
(2021-Jun) Pry JM; Manasyan A; Kapambwe S; Taghavi K; Duran-Frigola M; Mwanahamuntu M; Sikazwe I; Matambo J; Mubita J; Lishimpi K; Malama K; Bolton Moore C; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Pediatrics, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Internal Medicine, School of Medicine, Washington University, St Louis, MO, USA. Electronic address: jakepry@cidrz.org.; Ministry of Health, Lusaka, Zambia; University Teaching Hospital, Women and Newborn Hospital, Lusaka, Zambia.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; The Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; Ministry of Health, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona, Spain; Ersilia Open Source, Cambridge, UK.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Globally, cervical cancer is the fourth leading cause of cancer-related death among women. Poor uptake of screening services contributes to the high mortality. We aimed to examine screening frequency, predictors of screening results, and patterns of sensitisation strategies by age group in a large, programmatic cohort. METHODS: We did a cohort study including 11 government health facilities in Lusaka, Zambia, in which we reviewed routine programmatic data collected through the Cervical Cancer Prevention Program in Zambia (CCPPZ). Participants who underwent cervical cancer screening in one of the participating study sites were considered for study inclusion if they had a screening result. Follow-up was accomplished per national guidelines. We did descriptive analyses and mixed-effects logistic regression for cervical cancer screening results allowing random effects at the individual and clinic level. FINDINGS: Between Jan 1, 2010, and July 31, 2019, we included 183 165 women with 204 225 results for visual inspection with acetic acid and digital cervicography (VIAC) in the analysis. Of all those screened, 21 326 (10·4%) were VIAC-positive, of whom 16 244 (76·2%) received treatment. Of 204 225 screenings, 92 838 (45·5%) were in women who were HIV-negative, 76 607 (37·5%) were in women who were HIV-positive, and 34 780 (17·0%) had an unknown HIV status. Screening frequency increased 65·7% between 2010 and 2019 with most appointments being first-time screenings (n=158 940 [77·8%]). Women with HIV were more likely to test VIAC-positive than women who were HIV-negative (adjusted odds ratio 3·60, 95% CI 2·14-6·08). Younger women (≤29 years) with HIV had the highest predictive probability (18·6%, 95% CI 14·2-22·9) of screening positive. INTERPRETATION: CCPPZ has effectively increased women's engagement in screening since its inception in 2006. Customised sensitisation strategies relevant to different age groups could increase uptake and adherence to screening. The high proportion of screen positivity in women younger than 20 years with HIV requires further consideration. Our data are not able to discern if women with HIV have earlier disease onset or whether this difference reflects misclassification of disease in an age group with a higher sexually transmitted infection prevalence. These data inform scale-up efforts required to achieve WHO elimination targets. FUNDING: US President's Emergency Plan for AIDS Relief.
Characteristics and outcomes of adolescents living with perinatally acquired HIV within Southern Africa.
(2020-Dec-01) Tsondai PR; Braithwaite K; Fatti G; Bolton Moore C; Chimbetete C; Rabie H; Phiri S; Sawry S; Eley B; Hobbins MA; Boulle A; Taghavi K; Sohn AH; Davies MA; Newlands Clinic, Harare, Zimbabwe.; Harriet Shezi Children's Clinic, Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Faculty of Health Sciences, Johannesburg.; Lighthouse Trust Clinic, Lilongwe, Malawi.; Kheth' Impilo, AIDS Free Living, Cape Town.; Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg.; Red Cross War Memorial Children's Hospital and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.; TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand.; Department of Medicine, University of Alabama at Birmingham, Alabama, USA.; Department of Pediatrics and Child Health, Tygerberg Hospital, Stellenbosch University, Parow, South Africa.; Centre for Infectious Disease Epidemiology & Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town.; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.; Research & Quality Unit, SolidarMed, Lucerne.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Using data from 15 International epidemiology Databases to Evaluate AIDS in Southern Africa sites, we compared the characteristics and outcomes of adolescents living with perinatally acquired HIV (ALPH). METHODS: We included ALPH entering care aged less than 13 years with at least one HIV care visit during adolescence (10-19 years). We compared the characteristics and cross-sectional outcomes: transfer out, loss to follow-up (no visit in the 12 months prior to database closure), mortality, and retention between those who entered care aged less than 10 vs. aged 10-13 years; and explored predictors of mortality after age 13 years using Cox Proportional Hazards models. RESULTS: Overall, 16 229 (50% female) ALPH who entered HIV care aged less than 10 years and 8897 (54% female) aged 10-13 years were included and followed for 152 574 person-years. During follow-up, 94.1% initiated antiretroviral therapy, with those who entered care aged less than 10 more likely to have initiated antiretroviral therapy [97.9%, 95% confidence interval (CI) 97.6; 98.1%] than those who presented aged 10-13 years (87.3%, 95% CI 86.6; 88.0%). At the end of follow-up, 3% had died (entered care aged <10 vs. 10-13 years; 1.4 vs. 5.1%), 22% were loss to follow-up (16.2 vs. 33.4%), and 59% (66.4 vs. 45.4%) were retained. There was no difference in the risk of dying after the age of 13 years between adolescents entering care aged less than 10 vs. 10-13 years (adjusted hazard ratio 0.72; 95% CI 0.36; 1.42). CONCLUSION: Retention outcomes for ALPH progressively worsened with increasing age, with these outcomes substantially worse among adolescents entering HIV care aged 10-13 vs. less than 10 years.
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.
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.
Evaluation of kidney function among people living with HIV initiating antiretroviral therapy in Zambia.
(2022) Pry JM; Vinikoor MJ; Bolton Moore C; Roy M; Mody A; Sikazwe I; Sharma A; Chihota B; Duran-Frigola M; Daultrey H; Mutale J; Kerkhoff AD; Geng EH; Pollock BH; Vera JH; School of Medicine, University of California, Davis, California, United States of America.; School of Medicine University of Alabama, Birmingham, Alabama, United States of America.; Ersilia Open Source Initiative, Cambridge, United Kingdom.; School of Medicine, Washington University, St. Louis, Missouri, United States of America.; School of Medicine, University of California, San Francisco, California, United States of America.; Centre for Infectious Disease Research Zambia (CIDRZ), Lusaka, Zambia.; Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom.
As the response to the HIV epidemic in sub-Saharan Africa continues to mature, a growing number of people living with HIV (PLHIV) are aging and risk for non-communicable diseases increases. Routine laboratory tests of serum creatinine have been conducted to assess HIV treatment (ART) suitability. Here we utilize those measures to assess kidney function impairment among those initiating ART. Identification of non-communicable disease (NCD) risks among those in HIV care creates opportunity to improve public health through care referral and/or NCD/HIV care integration. We estimated glomerular filtration rates (eGFR) using routinely collected serum creatinine measures among a cohort of PLHIV with an HIV care visit at one of 113 Centre for Infectious Disease Research Zambia (CIDRZ) supported sites between January 1, 2011 and December 31, 2017, across seven of the ten provinces in Zambia. We used mixed-effect Poisson regression to assess predictors of eGFR <60ml/min/1.73m2 allowing random effects at the individual and facility level. Additionally, we assessed agreement between four eGFR formulae with unadjusted CKD-EPI as a standard using Scott/Fleiss method across five categories of kidney function. A total of 72,933 observations among 68,534 individuals met the inclusion criteria for analysis. Of the 68,534, the majority were female 41,042 (59.8%), the median age was 34 (interquartile range [IQR]: 28-40), and median CD4 cell count was 292 (IQR: 162-435). The proportion of individuals with an eGFR <60ml/min/1.73m2 was 6.9% (95% CI: 6.7-7.1%) according to the unadjusted CKD-EPI equation. There was variation in agreement across eGFR formulas considered compared to unadjusted CKD-EPI (χ2 p-value <0.001). Estimated GFR less than 60ml/min/1.73m2, per the unadjusted CKD-EPI equation, was significantly associated with age, sex, body mass index, and blood pressure. Using routine serum creatinine measures, we identified a significant proportion of individuals with eGFR indicating moderate or great kidney function impairment among PLHIV initiating ART in Zambia. It is possible that differentiated service delivery models could be developed to address this subset of those in HIV care with increased risk of chronic kidney disease.
Global Trends in CD4 Measurement and Immunosuppression at ART Initiation Among Children With HIV.
(2025-Apr-04) Patten G; Malateste K; Bolton Moore C; Sipambo N; Mokone L; Anderegg N; Wools-Kaloustian K; Michael D; Odhiambo F; Kasozi C; Desmonde S; Amorissani-Folquet M; Leroy V; Kumara Wati D; Nallusamy R; Kinikar A; Quy DT; Yotebieng M; Ebasone PV; Lelo P; Pinto J; Rouzier V; Machado DM; Haw NJ; Ford N; Department of Pediatrics, Prof. Dr. I.G.N.G. Ngoerah General Hospital, Udayana University, Bali, Indonesia.; School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.; Pediatric Department, Cocody University Hospital, Abidjan, Cote d'Ivoire.; Department of Medicine, Indiana University School of Medicine; Indianapolis, Indiana.; Department of Pediatrics, BJ Government Medical College and Sassoon General Hospital, Pune, India.; Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Kalembe Lembe Pediatric Hospital, Kinshasa, Democratic Republic of the Congo.; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.; Clinical Research Education, Networking and Consultancy (CRENC), Yaoundé, Cameroon.; Department of Pediatrics, Escola Paulista de Medicina, Federal University of Sao Paulo (UNIFESP), São Paulo, Brazil.; Centres GHESKIO, Port-au-Prince, Haiti.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.; SolidarMed, Maseru, Lesotho.; World Health Organization, Geneva, Switzerland.; Children's Hospital 1, Ho Chi Minh City, Vietnam.; University of Bordeaux, National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Research Centre, Bordeaux, France.; Department of Paediatrics and Child Health, Harriet Shezi Children's Clinic, Chris Hani Baragwanath Academic Hospital, University of Witwatersrand, Johannesburg, South Africa.; From the Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.; Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya.; Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.; Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), French National Institute for Health and Medical Research (Inserm), University of Toulouse 3, UMR 1295, Toulouse, France.; Department of Pediatrics, Penang Hospital, Penang, Malaysia.; Masaka Regional Referral Hospital, Masaka City, Uganda.; Tanzanian National Institute of Medical Research, Mwanza, Tanzania.
Eligibility for antiretroviral therapy is no longer based on immune criteria. In a global cohort of 97,453 children, between 2005 and 2021, we observed large declines in CD4 measurement, from 51% to 12% among <5 seconds, and from 74% to 20% among those 5-14 years of age. Lack of CD4 testing may negatively affect clinical care and surveillance of severe immune suppression.
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.
Impact of CYP2B6 genotype, tuberculosis therapy, and formulation on efavirenz pharmacokinetics in infants and children under 40 months of age.
(2022-Mar-15) Nikanjam M; Tran L; Chadwick EG; Bwakura-Dangarembizi M; Bolton Moore C; Samson P; Spector SA; Chakhtoura N; Jean-Philippe P; Frenkel L; Zimmer B; Benns A; Libous J; Capparelli EV; Maternal and Pediatric Infectious Disease Branch (MPIDB), Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health.; Department of Paediatrics and Child Health, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.; Frontier Science and Technology Research Foundation, Amherst, New York.; Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina.; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, California.; Department of Pediatrics, University of Washington, Seattle, Washington.; Department of Pediatrics, Northwestern University's Feinberg School of Medicine, Chicago, Illinois, USA.; Statistical and Data Management Center (SDMC) Harvard T.H. Chan School of Public Health, Center for Biostatistics in AIDS Research/Frontier Science Foundation, Boston, Massachusetts.; Division of AIDS, National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Centre for Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama.; IMPAACT Operations Center, FHI360, Durham, North Carolina, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: Dosing efavirenz (EFV) in children less than 3 years of age is challenging due to large variability in drug levels. This study evaluated differences in pharmacokinetics with tuberculosis (TB) therapy, formulation, age, and CYP2B6 genotype. DESIGN: Pharmacokinetic data from three IMPAACT/PACTG studies (P382, P1021, and P1070) for children initiating therapy less than 40 months of age were evaluated. METHODS: Pharmacokinetic data were combined in a population pharmacokinetic model. Exposure from the 2-week pharmacokinetic visit was compared with changes in viral RNA between the Week 0 and Week 4 visits. RESULTS: The model included 103 participants (19 on TB therapy). CYP2B6 516 genotype information was available for 82 participants (TT: 15, GT: 28, GG: 39). Median age at the first pharmacokinetic visit was 17.0 months (range: 2.0-39.0 months). Liquid formulation led to a 42% decrease in bioavailability compared with opened capsules. TB therapy (isoniazid and rifampin) led to a 29% decreased clearance, however Monte Carlo simulations demonstrated the majority of participants on TB therapy receiving standard EFV dosing to be in the target area under the curve range. Clearance was 5.3-fold higher for GG than TT genotype and 3.3-fold higher for GT than TT genotype. Age did not have a significant effect on clearance in the final model. Initial viral RNA decay was lower for patients in the lowest quartile of exposures (area under the curves) than for higher quartiles (P = 0.013). CONCLUSION: EFV dosing should account for CYP2B6 516 genotype and formulation, but does not require adjustment for concurrent TB therapy.
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.
Patient-reported reasons for declining same-day antiretroviral therapy initiation in routine HIV care settings in Lusaka, Zambia: results from a mixed-effects regression analysis.
(2020-Jul) Pry J; Chipungu J; Smith HJ; Bolton Moore C; Mutale J; Duran-Frigola M; Savory T; Herce ME; Division of Infectious Diseases, School of Medicine, Washington University, St. Louis, MO, USA.; Institute for Global Health & Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.; Implementation Science Unit, Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia.; Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain.; School of Medicine, University of Alabama, Birmingham, AL, USA.
INTRODUCTION: In the current "test and treat" era, HIV programmes are increasingly focusing resources on linkage to care and same-day antiretroviral therapy (ART) initiation to meet UNAIDS 95-95-95 targets. After observing sub-optimal treatment indicators in health facilities supported by the Centre for Infectious Disease Research in Zambia (CIDRZ), we piloted a "linkage assessment" tool in facility-based HIV testing settings to uncover barriers to same-day linkage to care and ART initiation among newly identified people living with HIV (PLHIV) and to guide HIV programme quality improvement efforts. METHODS: The one-page, structured linkage assessment tool was developed to capture patient-reported barriers to same-day linkage and ART initiation using three empirically supported categories of barriers: social, personal and structural. The tool was implemented in three health facilities, two urban and one rural, in Lusaka, Zambia from 1 November 2017 to 31 January 2018, and administered to all newly identified PLHIV declining same-day linkage and ART. Individuals selected as many reasons as relevant. We used mixed-effects logistic regression modelling to evaluate predictors of citing specific barriers to same-day linkage and ART, and Fisher's Exact tests to assess differences in barrier citation by socio-demographics and HIV testing entry point. RESULTS: A total of 1278 people tested HIV positive, of whom 126 (9.9%) declined same-day linkage and ART, reporting a median of three barriers per respondent. Of these 126, 71.4% were female. Females declining same-day ART were younger, on average, (median 28.5 years, interquartile range (IQR): 21 to 37 years) than males (median 34.5 years, IQR: 26 to 44 years). The most commonly reported barrier category was structural, "clinics were too crowded" (n = 33), followed by a social reason, "friends and family will condemn me" (n = 30). The frequency of citing personal barriers differed significantly across HIV testing point (χ CONCLUSIONS: Given differences observed in barriers to same-day ART initiation reported across sex, age, testing point, and facility type, new, tailored counselling and linkage to care approaches are needed, which should be rigorously evaluated in routine programme settings.
Pediatric HIV-HBV Coinfection in Lusaka, Zambia: Prevalence and Short-Term Treatment Outcomes.
(2015-Dec) Peebles K; Nchimba L; Chilengi R; Bolton Moore C; Mubiana-Mbewe M; Vinikoor MJ; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; Department of Pediatrics, University Teaching Hospital, Lusaka, Zambia.; Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA peebles.kathryn@gmail.com.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Hepatitis B virus (HBV) is endemic in Africa, where it may occur as an HIV coinfection. Data remain limited on HIV-HBV epidemiology in Africa, particularly in children. Using programmatic data from pediatric HIV clinics in Lusaka, Zambia during 2011-2014, we analyzed the prevalence of chronic HBV coinfection (defined as a single positive hepatitis B surface antigen [HBsAg] test) and its impact on immune recovery and liver enzyme elevation (LEE) during the first year of antiretroviral therapy. Among 411 children and adolescents, 10.4% (95% confidence interval, 7.6-14.1) had HIV-HBV. Coinfected patients were more likely to have World Health Organization stage 3/4, LEE and CD4 <14% at care entry (all p < 0.05). During treatment, CD4 increases and LEE incidence were similar by HBsAg status. HBsAg positivity decreased (11.8% vs. 6.6%; p = 0.24) following HBV vaccine introduction. These findings support screening pediatric HIV patients in Africa for HBV coinfection. Dedicated cohorts are needed to assess long-term outcomes of coinfection.
Resource Utilization and Costs of Care prior to ART Initiation for Pediatric Patients in Zambia.
(2014) Iyer HS; Scott CA; Lembela Bwalya D; Meyer-Rath G; Moyo C; Bolton Moore C; Larson BA; Rosen S; Zambia Center for Applied Health Research and Development, 10100 Lusaka, Zambia.; Center for Global Health and Development, Boston University, Boston, MA 02118, USA ; Health Economics and Epidemiology Research Office, Wits Health Consortium, Department of Clinical Medicine, School of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2198, South Africa.; Center for Global Health and Development, Boston University, Boston, MA 02118, USA ; Department of International Health, School of Public Health, Boston University, Boston, MA 02118, USA.; Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA ; Centre for Infectious Disease Research in Zambia, 101000 Lusaka, Zambia.; Zambia Center for Applied Health Research and Development, 10100 Lusaka, Zambia ; Center for Global Health and Development, Boston University, Boston, MA 02118, USA.; Zambian Ministry of Health, 10100 Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Objective. We estimated time to initiation, outpatient resource use, and costs of outpatient care during the 6 months prior to ART initiation for HIV-infected pediatric patients in Zambia. Methods. We enrolled 1,102 children who initiated ART at <15 years of age between 2006 and 2011 at 5 study sites. Of these, 832 initiated ART ≤6 months after first presenting to care at the study sites. Data on time in care and resources utilized during the 6 months prior to ART initiation were extracted from patient medical records. Costs were estimated from the provider's perspective and are reported in 2011 USD. Results. For the patients who initiated ART ≤6 months after presenting to care, median age at presentation to care was 3.9 years; median CD4 percentage was 13%. Median time to ART initiation was 26 days. Patients made, on average, 2.38 clinic visits prior to ART initiation and received 0.81 CD4 tests, 0.74 full blood count tests, and 0.49 blood chemistry tests. The mean cost of pre-ART care was $20 per patient. Conclusions. Zambian pediatric patients initiating ART ≤6 months after presenting to care do so quickly, utilize fewer resources than mandated by national guidelines, and accrue low costs.
Safety and pharmacokinetics of oral and long-acting injectable cabotegravir or long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study.
(2024-Apr) Gaur AH; Capparelli EV; Calabrese K; Baltrusaitis K; Marzinke MA; McCoig C; Van Solingen-Ristea RM; Mathiba SR; Adeyeye A; Moye JH; Heckman B; Lowenthal ED; Ward S; Milligan R; Samson P; Best BM; Harrington CM; Ford SL; Huang J; Crauwels H; Vandermeulen K; Agwu AL; Smith-Anderson C; Camacho-Gonzalez A; Ounchanum P; Kneebone JL; Townley E; Bolton Moore C; University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Janssen Research and Development, Beerse, Belgium.; Frontier Science Foundation, Boston, MA, USA.; FHI 360, Durham, NC, USA.; University of Colorado School of Medicine, Aurora, CO, USA.; Emory University School of Medicine-Children's Healthcare of Atlanta, Atlanta, GA, USA.; ViiV Healthcare, ResearchTriangle Park, NC, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; University of Alabama, Birmingham, AL, USA.; ViiV Healthcare, Madrid, Spain.; Baragwanath Academic Hospital, Johannesburg, South Africa.; Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Frontier Science Foundation, Amherst, NY, USA.; Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand.; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.; Johns Hopkins University School of Medicine, Baltimore, MD, USA.; University of California San Diego, La Jolla, CA, USA.; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA.; St Jude Children's Research Hospital, Memphis, TN, USA. Electronic address: aditya.gaur@stjude.org.; GlaxoSmithKline, Mississauga, ON, Canada.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Combined intramuscular long-acting cabotegravir and long-acting rilpivirine constitute the first long-acting combination antiretroviral therapy (ART) regimen approved for adults with HIV. The goal of the IMPAACT 2017 study (MOCHA [More Options for Children and Adolescents]) was to assess the safety and pharmacokinetics of these drugs in adolescents. METHODS: In this phase 1/2, multicentre, open-label, non-comparative, dose-finding study, virologically suppressed adolescents (aged 12-17 years; weight ≥35 kg; BMI ≤31·5 kg/m FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled: 30 in cohort 1C and 25 in cohort 1R. At week 16, 28 (97%, 95% CI 82-100) of the 29 dose-evaluable participants in cohort 1C and 21 (91%; 72-99) of the 23 dose-evaluable participants in cohort 1R had reported at least one adverse event, with the most common being injection-site pain (nine [31%] in cohort 1C; nine [39%] in cohort 1R; none were severe). One (4%, 95% CI 0-22) participant in cohort 1R had an adverse event of grade 3 or higher, leading to treatment discontinuation, which was defined as acute rilpivirine-related allergic reaction (self-limiting generalised urticaria) after the first oral dose. No deaths or life-threatening events occurred. In cohort 1C, the week 2 median cabotegravir AUC INTERPRETATION: Study data support using long-acting cabotegravir or long-acting rilpivirine, given every 4 weeks or 8 weeks, per the adult dosing regimens, in virologically suppressed adolescents aged 12 years and older and weighing at least 35 kg. FUNDING: The National Institutes of Health and ViiV Healthcare.
Understanding preferences for HIV care and treatment in Zambia: Evidence from a discrete choice experiment among patients who have been lost to follow-up.
(2018-Aug) Zanolini A; Sikombe K; Sikazwe I; Eshun-Wilson I; Somwe P; Bolton Moore C; Topp SM; Czaicki N; Beres LK; Mwamba CP; Padian N; Holmes CB; Geng EH; University of California, San Francisco, San Francisco, California, United States of America.; University of California, Berkeley, Berkeley, California, United States of America.; Georgetown University, Washington D.C., United States of America.; James Cook University, Townsville, Australia.; United Kingdom Department for International Development, Dar Es Salaam office, Dar Es Salaam, Tanzania.; 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: In public health HIV treatment programs in Africa, long-term retention remains a challenge. A number of improvement strategies exist (e.g., bring services closer to home, reduce visit frequency, expand hours of clinic operation, improve provider attitude), but implementers lack data about which to prioritize when resource constraints preclude implementing all. We used a discrete choice experiment (DCE) to quantify preferences for a number of potential clinic improvements to enhance retention. METHODS AND FINDINGS: We sought a random sample of HIV patients who were lost to follow-up (defined as >90 days late for their last scheduled appointment) from treatment facilities in Lusaka Province, Zambia. Among those contacted, we asked patients to choose between 2 hypothetical clinics in which the following 5 attributes of those facilities were varied: waiting time at the clinic (1, 3, or 5 hours), distance from residence to clinic (5, 10, or 20 km), ART supply given at each refill (1, 3, or 5 months), hours of operation (morning only, morning and afternoon, or morning and Saturday), and staff attitude ("rude" or "nice"). We used mixed-effects logistic regression to estimate relative utility (i.e., preference) for each attribute level. We calculated how much additional waiting time or travel distance patients were willing to accept in order to obtain other desired features of care. Between December 9, 2015 and May 31, 2016, we offered the survey to 385 patients, and 280 participated (average age 35; 60% female). Patients exhibited a strong preference for nice as opposed to rude providers (relative utility of 2.66; 95% CI 1.9-3.42; p < 0.001). In a standard willingness to wait or willingness to travel analysis, patients were willing to wait 19 hours more or travel 45 km farther to see nice rather than rude providers. An alternative analysis, in which trade-offs were constrained to values actually posed to patients in the experiment, suggested that patients were willing to accept a facility located 10 km from home (as opposed to 5) that required 5 hours of waiting per visit (as opposed to 1 hour) and that dispensed 3 months of medications (instead of 5) in order to access nice (as opposed to rude) providers. This study was limited by the fact that attributes included in the experiment may not have captured additional important determinants of preference. CONCLUSIONS: In this study, patients were willing to expend considerable time and effort as well as accept substantial inconvenience in order to access providers with a nice attitude. In addition to service delivery redesign (e.g., differentiated service delivery models), current improvement strategies should also prioritize improving provider attitude and promoting patient centeredness-an area of limited policy attention to date.