Browsing by Author "Bolton, Carolyn"

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An exploration of multi-level factors affecting routine linkage to HIV care in Zambia's PEPFAR-supported treatment program in the treat all era.
(2024) Chipungu, Jenala; Smith, Helene; Mwamba, Chanda; Haambokoma, Mwiza; Sharma, Anjali; Savory, Theodora; Musheke, Maurice; Pry, Jake; Bolton, Carolyn; Sikazwe, Izukanji; Herce, Michael E.
Multiple steps from HIV diagnosis to treatment initiation and confirmed engagement with the health system are required for people living with HIV to establish full linkage to care in the modern treat all era. We undertook a qualitative study to gain an in-depth understanding of the impeding and enabling factors at each step of this linkage pathway. In-depth interviews were conducted with fifty-eight people living with HIV recruited from ten routine HIV care settings supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) in Lusaka, Zambia. Using a semi-structured interview guide informed by an established conceptual framework for linkage to care, questions explored the reasons behind late, missed, and early linkage into HIV treatment, as well as factors influencing the decision to silently transfer to a different clinic after an HIV diagnosis. We identified previously established and intersecting barriers of internal and external HIV-related stigma, concerns about ART side effects, substance use, uncertainties for the future, and a perceived lack of partner and social support that impeded linkage to care at every step of the linkage pathway. However, we also uncovered newer themes specific to the current test and treat era related to the rapidity of ART initiation and insufficient patient-centered post-test counseling that appeared to exacerbate these well-known barriers, including callous health workers and limited time to process a new HIV diagnosis before treatment. Long travel distance to the clinic where they were diagnosed was the most common reason for silently transferring to another clinic for treatment. On the other hand, individual resilience, quality counseling, patient-centered health workers, and a supportive and empathetic social network mitigated these barriers. These findings highlight potential areas for strengthening linkage to care and addressing early treatment interruption and silent transfer in the test and treat era in Zambia.
Cardiovascular Involvement in Tuberculosis Patients Treated in Southern Africa.
(2025-Jan) Samim, Daryoush; Muula, Guy; Banholzer, Nicolas; Chibomba, Douglas; Xulu, Sihle ; Bolton, Carolyn; Evans, Denise; Perrig, Lisa; De Marchi, Stefano ; Günther, Gunar; Egger, Matthias; Pilgrim, Thomas; Fenner, Lukas
BACKGROUND: Tuberculosis (TB) is the leading cause of death among people with HIV and a major global health challenge. Subclinical cardiovascular manifestations of TB are poorly documented in high TB and HIV burden countries. OBJECTIVES: The purpose of this study was to quantify the prevalence of cardiovascular involvement in TB patients and investigate changes after completion of anti-TB treatment. METHODS: HIV-positive and HIV-negative patients diagnosed with pulmonary TB between October 2022 and November 2023 were enrolled from 2 tertiary care hospitals in Zambia and South Africa. Standardized transthoracic echocardiography (TTE) was conducted at TB diagnosis and after 6 months of anti-TB treatment. Cross-sectional and longitudinal analyses assessed pericardial effusion, thickening, or calcification, with and without signs of pericardial constriction. RESULTS: A total of 286 TB patients (218 [76%] men, 109 [38%] people with HIV, median age 35 years) underwent TTE at TB diagnosis, of whom 105 participants had a second TTE after completion of treatment. At TB diagnosis, 134 (47%) had pericardial effusions, 86 (30%) thickening, 7 (2%) calcifications, 103 (42%) signs of constriction, and 13 (12%) had definite diagnosis of constriction. After TB treatment, pericardial effusions (47% vs 16%, CONCLUSIONS: Cardiac involvement is frequent in newly diagnosed TB patients. Early pericardial changes may be reversed with anti-TB treatment. Echocardiographic screening facilitates early detection and timely management of cardiovascular involvement in TB patients.
Field evaluation of nanopore targeted next-generation sequencing to predict drug-resistant tuberculosis from native sputum in South Africa and Zambia.
(2025-Mar-12) Schwab, Tiana C.; Joseph, Lavania; Moono, Andrew; Göller, Pauline C.; Motsei, Mamello; Muula, Guy; Evans, Denise; Neuenschwander, Stefan; Günther, Gunar; Bolton, Carolyn; Keller, Peter M.; Ramette, Alban; Egger, Matthias; Omar, Shaheed V.; Fenner, Lukas
Rapid and comprehensive drug susceptibility testing (DST) is essential for diagnosing and treating drug-resistant tuberculosis effectively, and next-generation sequencing can be an effective genotypic DST method. We implemented and evaluated the performance of a nanopore targeted sequencing assay, called the Tuberculosis Drug Resistance Test (TBDR, Oxford Nanopore Diagnostics, Ltd., United Kingdom), which predicts drug resistance to 16 TB drugs, at a South African reference laboratory and a district diagnostic laboratory in Zambia. We compared the sequencing success rates between unprocessed and decontaminated sputum samples and determined the diagnostic accuracy against local DST (Xpert MTB/RIF Ultra, Xpert MTB/XDR, and BD BACTEC MGIT phenotypic DST). We prospectively sequenced 236 samples and have 148 samples with sequencing results from unprocessed and decontaminated sputum. We obtained successful sequencing results from 66.4% (94/148) unprocessed sputum samples and 75% (111/148) decontaminated samples. Sequencing success rates at the two sites differed, with 50.7% (36/71) successful sequencing results from unprocessed sputum in Zambia and 75.3% (58/77) in South Africa. Samples with "low" bacterial load, measured by Xpert MTB/RIF Ultra, tended to produce fewer successful sequencing results. TBDR sequencing predicted resistances in 48 samples, detecting resistance for rifampicin (
Mental, physical, and respiratory health in people with tuberculosis in Southern Africa: a multi-country cohort analysis.
(2025-Aug-20) Banholzer, Nicolas; Muula, Guy; Mureithi, Fiona; Evans, Denise; Huwa, Jacqueline; Rafael, Idiovino ; Kunzekwenyika, Cordelia; Jinga, Nelly; Fernando, Amina; Thawani, Agness; Schmutz, Remo; Bolton, Carolyn; Günther, Gunar; Egger, Matthias ; Haas, Andreas D.; Sweetland, Annika C.; Ballif, Marie; Fenner, Lukas
BACKGROUND: Tuberculosis (TB) affects people's quality of life (QoL). We prospectively monitored physical and mental health-related QoL over time in people with TB in the Southern African region with a high HIV and TB burden. METHODS: Adults aged ≥ 15 years with pulmonary TB were enrolled in five cohorts in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe from October 2022 to September 2024. We assessed six QoL outcomes using validated instruments at the start (baseline), end of treatment, and 6 months post-treatment: symptoms of depression (PHQ-9), mental and physical health (SF-12 mental, SF12-MC, SF-12 physical component, SF12-PC), physical fitness (6-Minute Walk Test, 6MWT; 1-min Sit-To-Stand Test, STST), and respiratory health (Saint-George-Respiratory-Questionnaire, SGRQ). Missing QoL scores were imputed with multivariate imputation by chained equations. We compared the proportion of participants with impaired QoL, defining impairment based on outcome-specific cut-off values. We also estimated changes in QoL scores and examined their associations with baseline characteristics using Bayesian multivariable regression models. RESULTS: We included 1438 participants with a median follow-up of 344 days (interquartile range [IQR] 183-373). The median age was 39 years (IQR 30-50); 67% were male, and 39% living with HIV. At baseline, 49% had symptoms of depression, 73% had impaired mental health and 92% impaired physical health-related QoL, 68-74% had reduced physical fitness (68%: 6MWT, 74%: STST), and 78% impaired respiratory health. All QoL outcomes improved by the end of treatment, notably depressive symptoms (48% to 5%), mental health-related QoL (73% to 28%), and respiratory health (78% to 11%). Most QoL impairments continued to decrease post-treatment, especially physical and respiratory health; depressive symptoms remained below 5%. Across QoL domains and study visits, better outcomes were associated with age < 30 (83% probability), and worse outcomes with female gender (86%) and a prior TB history (89%). Living with HIV and alcohol drinking were associated with worse QoL only at baseline (88% and 87%). CONCLUSIONS: TB negatively impacts QoL across physical, mental, and social domains, including post-treatment. The study highlights the need for integrated mental and physical healthcare and rehabilitation during TB treatment and beyond, especially for high-risk populations, to address the long-term impact of TB on QoL.
Patterns of engagement in care during clients' first 12 months after HIV treatment initiation in Zambia: a retrospective cohort analysis using routinely collected data.
(2025-Aug-11) Benade, Mariet; Maskew, Mhairi; Chilembo, Phillip; Mwansa, Mwansa W.; Savory, Theodora; Nichols, Brooke; Bolton, Carolyn; Mulenga, Lloyd B ; Sivile, Suilanji; Zyambo, Khozya D. ; Rosen, Sydney
BACKGROUND: The first year after HIV treatment initiation or re-initiation is the period of highest risk of a treatment interruption or disengagement, yet little is known about the timing, patterns and effects of interruptions in the early treatment period. METHODS: Using routinely collected electronic medical record data from 543 Zambian facilities from 2018 to 2023, we described patterns of engagement during the first year of HIV treatment. We defined engagement patterns for months 0-6 and months 7-12 after initiation or reinitiation as (1) continuous (attended all scheduled clinic and medication pickup visits as planned; (2) cyclical (attended ≥1 visits late >28 days but returned to and remained in care) or (3) disengaged (missed a scheduled visit by >28 days and had no evidence of return). RESULTS: Our sample population comprised 159 429 adult participants (61% female, median age 33). Of the 513 322 interactions observed ≤12 months after initiation, 53% occurred as planned, 22% were late ≤28 days late, 9% were >28 days late, and 17% were scheduled but never attended. In 0-6 months after initiation, 51% clients were continuously engaged, 12% cyclically engaged and 33% disengaged. Two-thirds of disengagers (21% of cohort) did not return after the initiation visit. During months 7-12, most clients who had been continuously engaged in months 0-6 (54%) remained continuous, while 18% moved to cyclical engagement. Among cyclical engagers in months 0-6, nearly half (47%) moved to being continuously engaged by month 12. Only 34% of the study population remained engaged continuously by the end of the 12-month period. CONCLUSIONS: Fewer than 60% of clients initiating antiretroviral therapy care between 2018 and 2022 at Zambian facilities remained continuously engaged at month 6 and 34% at month 12. Cyclical engagement and frequent interruptions should be accepted as the norm and models of service delivery designed to accommodate them.
Programme science in action: lessons from an observational study of HIV prevention programming for key populations in Lusaka, Zambia.
(2024-Jul) Sikazwe, Izukanji; Musheke, Maurice; Chiyenu, Kanema ; Ngosa, Benard; Pry, Jake M.; Mulubwa, Chama; Zimba, Martin; Sakala, Martin; Sakala, Mphatso; Somwe, Paul; Nyirenda, Goodwin; Savory, Theodora; Bolton, Carolyn; Herce, Michael E.
INTRODUCTION: Optimizing uptake of pre-exposure prophylaxis (PrEP) for individuals at risk of HIV acquisition has been challenging despite clear scientific evidence and normative guidelines, particularly for key populations (KPs) such as men who have sex with men (MSM), female sex workers (FSWs), transgender (TG) people and persons who inject drugs (PWID). Applying an iterative Programme Science cycle, building on the effective programme coverage framework, we describe the approach used by the Centre for Infectious Disease Research in Zambia (CIDRZ) to scale up PrEP delivery and address inequities in PrEP access for KP in Lusaka, Zambia. METHODS: In 2019, CIDRZ partnered with 10 local KP civil society organizations (CSOs) and the Ministry of Health (MOH) to offer HIV services within KP-designated community safe spaces. KP CSO partners led KP mobilization, managed safe spaces and delivered peer support; MOH organized clinicians and clinical commodities; and CIDRZ provided technical oversight. In December 2021, we introduced a community-based intervention focused on PrEP delivery in venues where KP socialize. We collected routine programme data from September 2019 to June 2023 using programme-specific tools and the national electronic health record. We estimated the before-after effects of our intervention on PrEP uptake, continuation and equity for KP using descriptive statistics and interrupted time series regression, and used mixed-effects regression to estimate marginal probabilities of PrEP continuity. RESULTS: Most (25,658) of the 38,307 (67.0%) Key Population Investment Fund beneficiaries were reached with HIV prevention services at community-based venues. In total, 23,527 (61.4%) received HIV testing services, with 15,508 (65.9%) testing HIV negative and found PrEP eligible, and 15,241 (98.3%) initiating PrEP. Across all programme quarters and KP types, PrEP uptake was >90%. After introducing venue-based PrEP delivery, PrEP uptake (98.7% after vs. 96.5% before, p < 0.001) and the number of initiations (p = 0.014) increased significantly. The proportion of KP with ≥1 PrEP continuation visit within 6 months of initiation was unchanged post-intervention (46.7%, 95% confidence interval [CI]: 45.7%, 47.6%) versus pre-intervention (47.2%, 95% CI: 45.4%, 49.1%). CONCLUSIONS: Applying Programme Science principles, we demonstrate how decentralizing HIV prevention services to KP venues and safe spaces in partnership with KP CSOs enabled successful community-based PrEP delivery beyond the reach of traditional facility-based services.
Use of task-shifting to rapidly scale-up HIV treatment services: experiences from Lusaka, Zambia.
(2009-Jan-09) Morris, Mary B.; Tambatamba-Chapula, Bushimbwa; Chi, Benjamin H.; Mwango, Albert; Chi, Harmony F.; Mwanza, Joyce; Manda, Handson; Bolton, Carolyn; Pankratz, Debra S.; Stringer, Jeffrey S.; Reid, Stewart E.
The World Health Organization advocates task-shifting, the process of delegating clinical care functions from more specialized to less specialized health workers, as a strategy to achieve the United Nations Millennium Development Goals. However, there is a dearth of literature describing task shifting in sub-Saharan Africa, where services for antiretroviral therapy (ART) have scaled up rapidly in the face of generalized human resource crises. As part of ART services expansion in Lusaka, Zambia, we implemented a comprehensive task-shifting program among existing health providers and community-based workers. Training begins with didactic sessions targeting specialized skill sets. This is followed by an intensive period of practical mentorship, where providers are paired with trainers before working independently. We provide on-going quality assessment using key indicators of clinical care quality at each site. Program performance is reviewed with clinic-based staff quarterly. When problems are identified, clinic staff members design and implement specific interventions to address targeted areas. From 2005 to 2007, we trained 516 health providers in adult HIV treatment; 270 in pediatric HIV treatment; 341 in adherence counseling; 91 in a specialty nurse "triage" course, and 93 in an intensive clinical mentorship program. On-going quality assessment demonstrated improvement across clinical care quality indicators, despite rapidly growing patient volumes. Our task-shifting strategy was designed to address current health care worker needs and to sustain ART scale-up activities. While this approach has been successful, long-term solutions to the human resource crisis are also urgently needed to expand the number of providers and to slow staff migration out of the region.
Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia.
(2025-Feb-05) Skrivankova, Veronika W.; Huwa, Jacquelin; Muula, Guy; Chiwaya, Geldert D.; Banda, Esau ; Buleya, Shameem; Chihota, Belinda; Chintedza, Joseph; Bolton, Carolyn; Tweya, Hannock; Kalua, Thokozani; Hossmann, Stefanie; Kouyos, Roger; Wandeler, Gilles; Egger, Matthias; Lessells, Richard J.
BACKGROUND: People with human immunodeficiency virus (PWH) on first-line, nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy (ART) were routinely switched to tenofovir-lamivudine-dolutegravir. We examined virologic outcomes and drug resistance in ART programs in Malawi, where switching was irrespective of viral load, and Zambia, where switching depended on a viral load <1000 copies/mL in the past year. METHODS: We compared the risk of viremia (≥400 copies/mL) at 1 and 2 years by viral load at switch and between countries using exact methods and logistic regression adjusted for age and sex. We performed HIV-1 pol Sanger sequencing on plasma samples with viral load ≥1000 copies/mL. RESULTS: A total of 2832 PWH were eligible (Malawi 1422, Zambia 1410); the median age was 37 years, and 2578 (91.0%) were women. At switch, 77 (5.4%) were viremic in Malawi and 42 (3.0%) in Zambia (P = .001). Viremia at switch was associated with viremia at 1 year (adjusted odds ratio (OR), 6.15; 95% confidence interval [CI], 3.13-11.4) and 2 years (7.0; 95% CI, 3.73-12.6). Viremia was less likely in Zambia than in Malawi at 1 year (OR, 0.55; 0.32-0.94) and 2 years (OR, 0.33; 0.18-0.57). Integrase sequencing was successful for 79 of 113 eligible samples. Drug resistance mutations were found in 5 PWH (Malawi 4, Zambia 1); 2 had major mutations (G118R, E138K, T66A and G118R, E138K) leading to high-level dolutegravir resistance. CONCLUSIONS: Restricting switching to dolutegravir-based ART to PWH with a viral load <1000 copies/mL may reduce subsequent viremia and, consequently, the emergence of dolutegravir drug resistance mutations. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov (NCT04612452).