Browsing by Author "Moore CB"

Now showing 1 - 18 of 18

Association between hepatitis B co-infection and elevated liver stiffness among HIV-infected adults in Lusaka, Zambia.
(2016-Nov) Vinikoor MJ; Mulenga L; Siyunda A; Musukuma K; Chilengi R; Moore CB; Chi BH; Davies MA; Egger M; Wandeler G
OBJECTIVE: To describe liver disease epidemiology among HIV-infected individuals in Zambia. METHODS: We recruited HIV-infected adults (≥18 years) at antiretroviral therapy initiation at two facilities in Lusaka. Using vibration controlled transient elastography, we assessed liver stiffness, a surrogate for fibrosis/cirrhosis, and analysed liver stiffness measurements (LSM) according to established thresholds (>7.0 kPa for significant fibrosis and >11.0 kPa for cirrhosis). All participants underwent standardised screening for potential causes of liver disease including chronic hepatitis B (HBV) and C virus co-infection, herbal medicine, and alcohol use. We used multivariable logistic regression to identify factors associated with elevated liver stiffness. RESULTS: Among 798 HIV-infected patients, 651 had a valid LSM (median age, 34 years; 53% female). HBV co-infection (12%) and alcohol use disorders (41%) were common and hepatitis C virus co-infection (<1%) was rare. According to LSM, 75 (12%) had significant fibrosis and 13 (2%) had cirrhosis. In multivariable analysis, HBV co-infection as well as male sex, increased age and WHO clinical stage 3 or 4 were independently associated with LSM >7.0 kPa (all P < 0.05). HBV co-infection was the only independent risk factor for LSM >11.0 kPa. Among HIV-HBV patients, those with elevated ALT and HBV viral load were more likely to have significant liver fibrosis than patients with normal markers of HBV activity. CONCLUSIONS: HBV co-infection was the most important risk factor for liver fibrosis and cirrhosis and should be diagnosed early in HIV care to optimise treatment outcomes.
Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi-country tracing study and linkage to a health information exchange.
(2024-Aug) Nyakato P; Schomaker M; Boulle A; Euvrard J; Wood R; Eley B; Prozesky H; Christ B; Anderegg N; Ayakaka I; Rafael I; Kunzekwenyika C; Moore CB; van Lettow M; Chimbetete C; Mbewe S; Ballif M; Egger M; Yiannoutsos CT; Cornell M; Davies MA
OBJECTIVES: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow-up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow-up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa. METHODS: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow-up were available from (1) a tracing study and (2) linkage to a health information exchange. For both populations, we compared six methods for correcting mortality estimates for all children, adolescents and young adults with HIV. RESULTS: We found substantial variations of mortality estimates among children, adolescents and young adults with HIV reported as lost to follow-up versus those retained in care. Ascertained mortality was higher among lost and traceable children, adolescents and young adults with HIV and lower among lost and linkable than those retained in care (mortality: 13.4% [traced] vs. 12.6% [retained-other Southern Africa countries]; 3.4% [linked] vs. 9.4% [retained-WC]). A high proportion of lost to follow-up children, adolescents and young adults with HIV had self-transferred (21.0% and 47.0%) in the traced and linked samples, respectively. The uncorrected method of non-informative censoring yielded the lowest mortality estimates among all methods for both tracing (6.0%) and linkage (4.0%) approaches at 2 years from ART start. Among corrected methods using ascertained data, multiple imputation, incorporating ascertained data (MI(asc.)) and inverse probability weighting with logistic weights were most robust for the tracing approach. In contrast, for the linkage approach, MI(asc.) was the most robust. CONCLUSIONS: Our findings emphasise that lost to follow-up is non-ignorable and both tracing and linkage improved outcome ascertainment: tracing identified substantial mortality in those reported as lost to follow-up, whereas linkage did not identify out-of-facility deaths, but showed that a large proportion of those reported as lost to follow-up were self-transfers.
Drug Resistance in People With Viremia on Dolutegravir-based Antiretroviral Therapy in Sub-Saharan Africa: The DTG RESIST Study.
(2025-May-20) Loosli T; Moore CB; Buzaalirwa L; Byakwaga H; Çelikağ İ; Chimbetete C; Ebasone PV; Giandhari J; Han N; Huwa J; Kasozi C; Mafoua A; Messou E; Minga A; Muula G; Muyindike W; Ndala ACM; Sauermann M; Semeere A; Singh L; Kouyos RD; Lessells R; Egger M
Dolutegravir resistance is an increasing concern. An analysis of the DTG RESIST study found that among 227 integrase sequences from 7 African countries (all non-B subtypes), 59 (26.0%) had at least 1 major drug resistance mutation (primarily G118R and E138A/K/T), with 49 (21.6%) predicted to have high-level resistance to dolutegravir.
Establishing Dosing Recommendations for Efavirenz in HIV/TB-Coinfected Children Younger Than 3 Years.
(2019-Aug-01) Bwakura Dangarembizi M; Samson P; Capparelli EV; Moore CB; Jean-Philippe P; Spector SA; Chakhtoura N; Benns A; Zimmer B; Purdue L; Jackson C; Wallis C; Libous JL; Chadwick EG
BACKGROUND: CYP2B6 516 genotype-directed dosing improves efavirenz (EFV) exposures in HIV-infected children younger than 36 months, but such data are lacking in those with tuberculosis (TB) coinfection. METHODS: Phase I, 24-week safety and pharmacokinetic (PK) study of EFV in HIV-infected children aged 3 to <36 months, with or without TB. CYP2B6 516 genotype classified children into extensive metabolizers (516 TT/GT) and poor metabolizers [(PMs), 516 TT]. EFV doses were 25%-33% higher in children with HIV/TB coinfection targeting EFV area under the curve (AUC) 35-180 μg × h/mL, with individual dose adjustment as necessary. Safety and virologic evaluations were performed every 4-8 weeks. RESULTS: Fourteen children from 2 African countries and India with HIV/TB enrolled, with 11 aged 3 to <24 months and 3 aged 24-36 months, 12 extensive metabolizers and 2 PMs. Median (Q1, Q3) EFV AUC was 92.87 (40.95, 160.81) μg × h/mL in 8/9 evaluable children aged 3 to <24 months and 319.05 (172.56, 360.48) μg × h/mL in children aged 24-36 months. AUC targets were met in 6/8 and 2/5 of the younger and older age groups, respectively. EFV clearance was reduced in PM's and older children. Pharmacokinetic modeling predicted adequate EFV concentrations if children younger than 24 months received TB-uninfected dosing. All 9 completing 24 weeks achieved viral suppression. Five/14 discontinued treatment early: 1 neutropenia, 3 nonadherence, and 1 with excessive EFV AUC. CONCLUSIONS: Genotype-directed dosing safely achieved therapeutic EFV concentrations and virologic suppression in HIV/TB-coinfected children younger than 24 months, but further study is needed to confirm appropriate dosing in those aged 24-36 months. This approach is most important for young children and currently a critical unmet need in TB-endemic countries.
Establishing shared definitions of virological failure and discontinuation for long-acting injectable cabotegravir and rilpivirine therapy (the CONSENSUS-LAI Study): an international survey and Delphi process.
(2025-Sep) Orkin C; Paterson A; Elias A; Smuk M; Ring K; Volny-Anne A; Calmy A; Hazra A; Geretti AM; Radix A; Titanji BK; Spire B; Del Rio C; Foster C; Moore CB; Cortes CP; Mussini C; Kuritzkes DR; Tan DHS; Martinez E; Wit FWNM; Cresswell F; Venter WDF; Levy I; Zucker J; Molina JM; Hoy J; Arribas J; Llibre JM; Currier J; Rockstroh J; Sutinen J; Gebo K; Waters L; Gisslen M; O'Reilly M; Boffito M; Thompson M; Parczewski M; John M; Gandhi M; Kumarasamy N; Paton N; Mackie N; Cahn P; Elion R; Noe S; Walmsley S; Collins S; Cole-Haley S; Apea V; Short WR; Gilleece Y; Paparini S
BACKGROUND: Definitions of virological failure and treatment discontinuation for long-acting injectable (LAI) cabotegravir and rilpivirine antiretroviral therapy are inconsistent in clinical practice and observational studies, which complicates interpretation and implementation of findings. The CONSENSUS-LAI study aimed to establish consistent definitions of virological failure and treatment discontinuation to enhance evidence transferability and support optimal clinical outcomes. METHODS: The study had two phases. Phase 1 was an international online survey exploring existing definitions of virological and treatment discontinuation, conducted between April 25 and July 1, 2024. Eligible participants were health-care professionals working in infectious disease or sexual health services who had provided care to at least ten people living with HIV in the past 6 months, had prescribed LAI cabotegravir and rilpivirine in clinical trials or clinical practice, and were able to give informed consent. Participants were recruited via social media and mailing lists of medical specialist societies. Phase 2 was a Delphi process, in which a panel of experts, selected to ensure representation from all six WHO regions, scored leading definitions from phase 1 on a 9-point Likert scale. The proposed definitions were scored according to four validity criteria: clarity, usability in the expert's setting, appropriateness across clinical purposes, and applicability across relevant population groups. Revisions were suggested in iterative rounds until consensus was reached. Consensus was predefined as at least 75% of experts agreeing or strongly agreeing (scores 7-9) with the validity criteria. FINDINGS: 386 LAI cabotegravir and rilpivirine prescribers across 28 countries completed the survey, revealing 15 definitions for virological failure on LAI cabotegravir and rilpivirine and nine for treatment discontinuation. 52 experts participated in the Delphi process. Consensus agreement on both definitions was reached after two rounds for all validity criteria. For virological failure, the consensus definition was as follows: (a) viral load 200 copies or more per mL or more on two occasions 2-4 weeks apart, or (b) a single viral load of more than 1000 copies per mL, and/or (c) emergent resistance, in the context of timely injections and prior suppression of less than 200 copies per mL, OR (d) unable to suppress viral load to less than 200 copies per mL on continuous therapy. For treatment discontinuation the consensus definition was as follows: people on LAI cabotegravir and rilpivirine who have missed two consecutive injections and have not taken oral bridging in the interim, irrespective of reason for discontinuation. INTERPRETATION: The consensus definitions provide a foundation for aligning practice and evaluating patient outcomes. Further validation of the viral load threshold for virological failure and the optimal viral load retesting window is required. FUNDING: ViiV Healthcare.
Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia.
(2022-Jan-10) Nyemba DC; Kalk E; Vinikoor MJ; Madlala HP; Mubiana-Mbewe M; Mzumara M; Moore CB; Slogrove AL; Boulle A; Davies MA; Myer L; Powis K
BACKGROUND: Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. METHODS: We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6-10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. RESULTS: Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6-10 weeks were lower among infants who were HEU vs HU [β = - 0.29 (95% CI: - 0.46, - 0.12) and [β = - 0.42 (95% CI: - 0.68, - 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [β = - 0.28 CI: - 0.50, - 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6-10 weeks, [β = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [β = - 0.30 CI: - 0.59, - 0.01)] at 6 months, without other anthropometric differences at either site. CONCLUSION: Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU.
Identifying care gaps along the HIV treatment failure cascade: A multistate analysis of viral load monitoring, re-suppression, and regimen switches in Zambia.
(2025-Sep) Sikombe K; Le Tourneau N; Rice B; Pry JM; Simbeza S; Beres LK; Sharma A; Mukamba N; Wringe A; Hargreaves JR; Mutale J; Moore CB; Sikazwe I; Geng E; Mody A
BACKGROUND: Timely response to treatment failure is critical for improved outcomes and viral re-suppression among people living with HIV, but care gaps along the treatment failure cascade can occur due to delays by both clients (e.g., retention and adherence) and health systems (e.g., fidelity to viral load [VL] monitoring guidelines). We used multistate analysis to identify drivers of implementation gaps in the treatment failure cascade, including time to HIV VL monitoring, re-suppression, and regimen switches, in Zambia. METHODS AND FINDINGS: We used national electronic HIV health records to identify adults on antiretroviral therapy (ART) for more than 6 months who experienced treatment failure (VL ≥ 1,000 copies/ml) at 24 clinics in Lusaka, Zambia, between August 2019 and November 2021. Using multistate analyses, we examined how care evolved after treatment failure, accounting for transitions across the treatment failure cascade over time, such as return visits, repeat VL testing, treatment interruptions (>60 days late for visit), and viral re-suppression. Analyses were stratified by ART regimen at cohort entry: tenofovir disoproxil fumarate/lamivudine or emtricitabine/dolutegravir TDF/XTC/DTG (TLD) and tenofovir disoproxil fumarate/lamivudine or emtricitabine/efavirenz TDF/XTC/EFV (TLE). We repeated analyses to assess switch to second-line therapy among those with consecutively unsuppressed VL test results who were due for regimen switch. Among 179,855 individuals on ART (143,857 with documented VL), 7,916 (4.4%) had a documented elevated VL and drug regimen at the time of treatment failure (52.3% female, median age was 36.7 years (IQR 29.9-43.6), median time on ART 3.3 years (IQR 1.7-6.6), 54.6% on TLD and 45.4% on TLE). Among those with treatment failure, 72.2% (CI 71.3, 73.0%) had returned to clinic 6 months after initial elevated VL was drawn. After one year, 70.1% (CI 69.3, 70.9%) had a repeat VL, 16.6% (CI 15.9, 17.2%) experienced treatment interruption, and 11.4% (CI 10.3, 12.4%) returned to care without repeat VL testing. Among those with a repeat VL, 85.0% (CI 83.9, 86.1%) on TLD and 58.2% (CI 56.8, 59.8%) on TLE had resuppressed. Among those due for second-line switch, 27.9% (CI 24.1, 31.5%) on TLD and 66.6% (CI 64.5, 68.9%) on TLE had changed regimens after one year while 52.4% on TLD had a third VL repeated prior to switch (CI 47.2, 57.4%) (68.0% CI 61.6, 75.2% suppressed of those with repeated VL) compared to 32.1% (CI 29.9, 34.1%) (40.7% CI 36.1, 45.4% suppressed) on TLE. This study was limited by the inability to capture all aspects of care delivery related to treatment failure, such as outreach, enhanced adherence counseling confirmation, and provider rationale for delayed VL rechecking. CONCLUSION: After treatment failure, we identified substantial delays in returning for adherence counseling, treatment interruptions, and missed opportunities in rechecking VL status or switching to second-line therapy in routine care in Zambia. Among those who did have VL tests rechecked, re-suppression rates were significantly higher among individuals on TLD compared to TLE. To optimize response and outcomes after treatment failure, strategies must prioritize and target both client and health systems behaviors to meet the care needs in the modern era of TLD.
Implementing SARS-CoV-2 routine surveillance in antenatal care in Zambia, 2021-2022: best practices and lessons learned.
(2025-Feb-28) Tembo T; Heilmann E; Kabamba BM; Fwoloshi S; Kalenga K; Chilambe F; Siwinga M; Rutagwera MR; Musunse M; Kangale C; Yingst S; Yadav R; Savory T; Gutman JR; Sikazwe I; Mulenga LB; Moore CB; Hines JZ
BACKGROUND: In Zambia, the true extent of SARS-CoV-2 infections is unknown because initial surveillance focused on patients with symptoms or severe disease. Antenatal sentinel surveillance had not been used to assess infection trends. The ANC COVID-19 surveillance study sought to determine SARS-CoV-2 seroprevalence and COVID-19 vaccine uptake among pregnant women. We provide insight into the study implementation, challenges encountered, best practices, and lessons learned. METHODS: A repeated cross-sectional seroprevalence survey was implemented at 39 health facilities in four districts from September 2021 to September 2022. Pregnant women aged 15-49 years were enrolled at their first antenatal care visits. An electronic questionnaire gathered demographics and other COVID-19 related information from consenting participants. A dried blood sample was collected to detect IgG antibodies using a multiplex bead assay. Seropositive results were categorized as infection, infection and vaccination or infection based on anti-RBD and anti-nucleocapsid test results. Problems and their root causes were identified as they occurred. Practical problem-solving strategies were devised, implemented, and monitored to ensure that goals were accomplished. RESULTS: In the primary analysis, 7% of the 9,221 samples collected from participants were not tested because they were missing. COVID-19 vaccine uptake of 9,111 pregnant women was assessed. Approximately 64% of participants were cumulatively seropositive for SARS-CoV-2 antibodies. Seroprevalence increased from 27.8% in September 2021 to 56.6% in July 2022. We observed an increase in vaccine coverage (0.5-27%) over time. Women aged 40-49 years old, without education and with prior COVID-19 infection were associated with higher vaccine uptake. The Delta variant of COVID-19 and the reallocation of health facilities between two partners delayed surveillance activities and increased the cost of implementation (e.g., the purchase of additional calibration and validation kits and DBS cards). Protocol deviations were attributed to the lack of experience in conducting research but, the district RAs repeatedly trained health facility staff to enhance their research knowledge. CONCLUSIONS: Incorporating SARS-CoV-2 surveillance into routine antenatal care is feasible and potentially sustainable when existing health system infrastructure, human resources, and surveillance systems are leveraged. Yet, careful planning is needed to anticipate implementation challenges and ensure high-quality data collection.
Managing multiple funding streams and agendas to achieve local and global health and research objectives: lessons from the field.
(2014-Jan-01) Holmes CB; Sikazwe I; Raelly RL; Freeman BL; Wambulawae I; Silwizya G; Topp SM; Chilengi R; Henostroza G; Kapambwe S; Simbeye D; Sibajene S; Chi H; Godfrey K; Chi B; Moore CB
Multiple funding sources provide research and program implementation organizations a broader base of funding and facilitate synergy, but also entail challenges that include varying stakeholder expectations, unaligned grant cycles, and highly variable reporting requirements. Strong governance and strategic planning are essential to ensure alignment of goals and agendas. Systems to track budgets and outputs, as well as procurement and human resources are required. A major goal of funders is to transition leadership and operations to local ownership. This article details successful approaches used by the newly independent nongovernmental organization, the Centre for Infectious Disease Research in Zambia.
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
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.
Patterns and Predictors of Incident Return to HIV Care Among Traced, Disengaged Patients in Zambia: Analysis of a Prospective Cohort.
(2021-Mar-01) Beres LK; Schwartz S; Simbeza S; McGready J; Eshun-Wilson I; Mwamba C; Sikombe K; Topp SM; Somwe P; Mody A; Mukamba N; Ehrenkranz PD; Padian N; Pry J; Moore CB; Holmes CB; Sikazwe I; Denison JA; Geng E
BACKGROUND: Dynamic movement of patients in and out of HIV care is prevalent, but there is limited information on patterns of patient re-engagement or predictors of return to guide HIV programs to better support patient engagement. METHODS: From a probability-based sample of lost to follow-up, adult patients traced by peer educators from 31 Zambian health facilities, we prospectively followed disengaged HIV patients for return clinic visits. We estimated the cumulative incidence of return and the time to return using Kaplan-Meier methods. We used univariate and multivariable Cox proportional hazards regression to conduct a risk factor analysis identifying predictors of incident return across a social ecological framework. RESULTS: Of the 556 disengaged patients, 73.0% [95% confidence interval (CI): 61.0 to 83.8] returned to HIV care. The median follow-up time from disengagement was 32.3 months (interquartile range: 23.6-38.9). The rate of return decreased with time postdisengagement. Independent predictors of incident return included a previous gap in care [adjusted Hazard Ratio (aHR): 1.95, 95% CI: 1.23 to 3.09] and confronting a stigmatizer once in the past year (aHR: 2.14, 95% CI: 1.25 to 3.65). Compared with a rural facility, patients were less likely to return if they sought care from an urban facility (aHR: 0.68, 95% CI: 0.48 to 0.96) or hospital (aHR: 0.52, 95% CI: 0.33 to 0.82). CONCLUSIONS: Interventions are needed to hasten re-engagement in HIV care. Early and differential interventions by time since disengagement may improve intervention effectiveness. Patients in urban and tertiary care settings may need additional support. Improving patient resilience, outreach after a care gap, and community stigma reduction may facilitate return. Future re-engagement research should include causal evaluation of identified factors.
"Provider discretionary power practices to support implementation of patient-centered HIV care in Lusaka, Zambia".
(2022) Mwamba C; Mukamba N; Sharma A; Lumbo K; Foloko M; Nyirenda H; Simbeza S; Sikombe K; Holmes CB; Sikazwe I; Moore CB; Mody A; Geng E; Beres LK
INTRODUCTION: Traditional patient-provider relationships privilege the providers, as they possess the formal authority and clinical knowledge applied to address illness, but providers also have discretion over how they exercise their power to influence patients' services, benefits, and sanctions. In this study, we assessed providers' exercise of discretionary power in implementing patient-centered care (PCC) practices in Lusaka, Zambia. METHODS: HIV clinical encounters between patients on antiretroviral therapy (ART) and providers across 24 public health facilities in Lusaka Province were audio recorded and transcribed verbatim. Using qualitative content analysis, we identified practices of discretionary power (DP) employed in the implementation of PCC and instances of withholding DP. A codebook of DP practices was inductively and iteratively developed. We compared outcomes across provider cadres and within sites over time. RESULTS: We captured 194 patient-provider interactions at 24 study sites involving 11 Medical Officers, 58 Clinical Officers and 10 Nurses between August 2019 to May 2021. Median interaction length was 7.5 min. In a hierarchy where providers dominate patients and interactions are rapid, some providers invited patients to ask questions and responded at length with information that could increase patient understanding and agency. Others used inclusive language, welcomed patients, conducted introductions, and apologized for delayed services, narrowing the hierarchical distance between patient and provider, and facilitating recognition of the patient as a partner in care. Although less common, providers shared their decision-making powers, allowing patients to choose appointment dates and influence regimens. They also facilitated resource access, including access to services and providers outside of scheduled appointment times. Application of DP was not universal and missed opportunities were identified. CONCLUSION: Supporting providers to recognize their power and intentionally share it is both inherent to the practice of PCC (e.g., making a patient a partner), and a way to implement improved patient support. More research is needed to understand the application of DP practices in improving the patient-centeredness of care in non-ART settings.
Provider perspectives on patient-centredness: participatory formative research and rapid analysis methods to inform the design and implementation of a facility-based HIV care improvement intervention in Zambia.
(2023-Jul) Mwamba C; Beres LK; Mukamba N; Jere L; Foloko M; Lumbo K; Sikombe K; Simbeza S; Mody A; Pry JM; Holmes CB; Sikazwe I; Moore CB; Christopoulos K; Sharma A; Geng EH
INTRODUCTION: Implementation of patient-centred care (PCC) practices in HIV treatment depends on healthcare workers' (HCWs) perceptions of the acceptability, appropriateness and feasibility of such practices (e.g. use of intentional, metric-driven activities to improve patient experiences). METHODS: We applied rapid, rigorous formative research methods to refine a PCC intervention for future trial. In 2018, we conducted focus group discussions (FGDs) with 46 HCWs purposefully selected from two pilot sites. We elicited HCW perceptions of HIV service delivery, HCW motivation and perceived value of patient experience measures intended to improve PCC. FGDs utilized participatory methods to understand HCW responses to patient-reported care engagement challenges and Scholl's PCC Framework principles (e.g. seeing a patient as a unique person), enablers (e.g. care coordination) and activities (e.g. patient involvement). Our rapid analysis used analytic memos, thematic analysis, research team debriefs and HCW feedback to inform time-sensitive trial implementation. RESULTS: While HCWs nearly universally identified with and supported principles of PCC in both facilities, they raised practical barriers given the practice environment. HCWs described motivation to help patients, attached value to seeing positive health outcomes and the importance of teamwork. However, HCWs reported challenges with enablers needed to deliver PCC. HCWs cited a work culture characterized by differential power dynamics between cadres and departments restricting HCW autonomy and resource access. Barriers included inflexibility in accommodating individual patient needs due to high patient volumes, limited human resources, laboratory capacity, infrastructure and skills translating patient perspectives into practice. HCW motivation was negatively influenced by encounters with "difficult patients," and feeling "unappreciated" by management, resulting in cognitive dissonance between HCW beliefs and behaviours. However, the enactment of PCC values also occurred. Results suggested that PCC interventions should reduce practice barriers, highlighting the value of mentors who could help HCWs dynamically engage with health system constraints, to facilitate PCC. CONCLUSIONS: While HCWs perceived PCC principles as acceptable, they did not think it universally appropriate or feasible given the practice environment. Participatory and rapid methods provided timely insight that PCC interventions must provide clear and effective systems enabling PCC activities by measuring and mitigating relational and organizational constraints amenable to change such as inter-cadre coordination.
Quality of Care and Service Expansion for HIV Care and Treatment.
(2015-Jun) Moore CB; Ciaraldi E
The last two decades have seen exceptional development of antiretroviral treatment programs throughout the world. Over 14 million persons are accessing antiretroviral treatment (ART) treatment as of early 2015, and life expectancy has risen markedly in the most-affected populations. However, large patient numbers threaten to overwhelm already over-burdened health care systems and retention in care remains suboptimal. Developing innovative strategies to alleviate these burdens and retain patients in care remains a challenge. Furthermore, despite this expansion, large populations of HIV-infected persons remain undiagnosed and are unwilling or unable to access care and treatment programs. Marginalized and high-risk populations are particularly in danger of remaining outside of care and are also disproportionately affected by HIV. To reverse the trend and "fast track" our way out of the epidemic, ambitious treatment targets are required, and a concerted effort has to be made to engage these populations into care, initiate ART, and attain viral suppression.
Redefining and revisiting cost estimates of routine ART care in Zambia: an analysis of ten clinics.
(2020-Feb) Tucker A; Tembo T; Tampi RP; Mutale J; Mukumba-Mwenechanya M; Sharma A; Dowdy DW; Moore CB; Geng E; Holmes CB; Sikazwe I; Sohn H
INTRODUCTION: Accurate costing is key for programme planning and policy implementation. Since 2011, there have been major changes in eligibility criteria and treatment regimens with price reductions in ART drugs, programmatic changes resulting in clinical task-shifting and decentralization of ART delivery to peripheral health centres making existing evidence on ART care costs in Zambia out-of-date. As decision makers consider further changes in ART service delivery, it is important to understand the current drivers of costs for ART care. This study provides updates on costs of ART services for HIV-positive patients in Zambia. METHODS: We evaluated costs, assessed from the health systems perspective and expressed in 2016 USD, based on an activity-based costing framework using both top-down and bottom-up methods with an assessment of process and capacity. We collected primary site-level costs and resource utilization data from government documents, patient chart reviews and time-and-motion studies conducted in 10 purposively selected ART clinics. RESULTS: The cost of providing ART varied considerably among the ten clinics. The average per-patient annual cost of ART service was $116.69 (range: $59.38 to $145.62) using a bottom-up method and $130.32 (range: $94.02 to $162.64) using a top-down method. ART drug costs were the main cost driver (67% to 7% of all costs) and are highly sensitive to the types of patient included in the analysis (long-term vs. all ART patients, including those recently initiated) and the data sources used (facility vs. patient level). Missing capacity costs made up 57% of the total difference between the top-down and bottom-up estimates. Variability in cost across the ten clinics was associated with operational characteristics. CONCLUSIONS: Real-world costs of current routine ART services in Zambia are considerably lower than previously reported estimates and sensitive to operational factors and methods used. We recommend collection and monitoring of resource use and capacity data to periodically update cost estimates.
Safety of combined long-acting injectable cabotegravir and 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.
(2025-Mar) Moore CB; Baltrusaitis K; Best BM; Moye JH; Townley E; Violari A; Heckman B; Buisson S; Van Solingen-Ristea RM; Capparelli EV; Marzinke MA; Lowenthal ED; Ward S; Krotje C; Milligan R; Agwu AL; Huang J; Cheung SYA; McCoig C; Yin DE; Roberts G; Crauwels H; Van Eygen V; Zabih S; Masheto G; Ounchanum P; Aurpibul L; Korutaro V; Gaur AH
BACKGROUND: Long-acting cabotegravir and long-acting rilpivirine constitute a completely intramuscular antiretroviral therapy (ART) regimen for adults with HIV. We aimed to assess the safety, antiviral activity, and pharmacokinetics of oral cabotegravir and rilpivirine followed by a combination of long-acting cabotegravir and long-acting rilpivirine in virologically suppressed adolescents with HIV. METHODS: The IMPAACT 2017/MOCHA study is a phase 1/2, multicentre, open-label, non-comparative, dose-finding trial being conducted at 18 sites across Botswana, South Africa, Thailand, Uganda, and the USA. In cohort 2 of this study, adolescents (aged 12-18 years; weight ≥35 kg) with HIV and no serious comorbidities who were receiving stable combination ART with confirmed virological suppression and had either previously enrolled in the first cohort or had not previously participated in the study were eligible for inclusion. Participants stopped their background combination ART and received oral cabotegravir 30 mg once daily and oral rilpivirine 25 mg once daily orally for 4-6 weeks, followed by long-acting injectable cabotegravir 600 mg (3 mL) and long-acting injectable rilpivirine 900 mg (3 mL) intramuscularly at weeks 4 and 8, and every 8 weeks thereafter. The primary outcome was safety, including all adverse events, at week 24. Primary safety outcome measures were summarised as frequencies, percentages, and exact Clopper-Pearson 95% CIs in the evaluable analysis population, which included participants who were treated exclusively with the regimen and either completed all scheduled treatments or experienced severe adverse events, permanently discontinued the treatment, or died, whichever occurred first; and in the all-treated analysis population, which included all participants who received at least one dose of any study product. This study is registered with ClinicalTrials.gov (NCT3497676) and is ongoing. FINDINGS: Between July 26, 2021, and Aug 27, 2022, 44 (80·0%) of 55 adolescents who participated in cohort 1 and 100 (87·0%) of 115 screened study-naive adolescents were enrolled in cohort 2. 74 (51·4%) participants were female and 70 (48·6%) were male. Overall, 15 (10·8% [95% CI 6·2-17·2]) of all 139 participants in the evaluable analysis population had at least one adverse event of grade 3 or above by week 24. Among 142 participants who received at least one injection, 43 (30%) experienced at least one injection site reaction (ISR). All 106 ISRs were either grade 1 (98 [92·5%]) or grade 2 (eight [7·5%]), and 97 (91·5%) resolved within 7 days. No participant experienced a drug-related serious adverse event or prematurely discontinued treatment due to a drug-related adverse event. INTERPRETATION: Long-acting injectable cabotegravir and long-acting injectable rilpivirine, administered to adolescents at recommended adult dosages every 8 weeks, showed no unanticipated safety concerns in the 24 weeks following administration. FUNDING: National Institutes of Health, ViiV Healthcare, and Johnson & Johnson.
Scale of differentiated service delivery implementation in HIV care facilities in low- and middle-income countries: a global facility survey.
(2025-Jul) Fernández Villalobos NV; Helfenstein F; Khol V; Twizere C; Secco M; Castelnuovo B; Huwa J; Tiendredbeogo T; Wester CW; Fong SM; Murenzi G; Caro-Vega Y; Lyamuya RE; Rafael I; Zannou DM; Petoumenos K; Nsonde DM; Pinto J; Wools-Kaloustian K; Moore CB; Takassi OE; Kiertiburanakul S; Awoh RA; Ali SM; Fatti G; Malateste K; Zaniewski E; Ballif M
INTRODUCTION: In 2016, the World Health Organization recommended differentiated service delivery (DSD) as a client-centred approach to simplify HIV care in frequency and intensity, thus reducing the clinic visit burden on individuals and HIV programmes. We describe the scale of DSD implementation among HIV facilities in low- and middle-income countries (LMICs) in Latin America, Africa and the Asia-Pacific before the COVID-19 pandemic. METHODS: We analysed facility-level survey data from HIV care facilities participating in the International epidemiology Databases to Evaluate AIDS consortium in 2019. We used descriptive statistics to summarise the availability of DSD, multi-month dispensing (MMD) and DSD for HIV treatment models. We explored factors associated with DSD implementation using multivariable models. RESULTS: We included 175 facilities in the Asia-Pacific (n = 30), Latin America (n = 8), Central Africa (n = 21), East Africa (n = 74), Southern Africa (n = 28) and West Africa (n = 14). Overall, 133 facilities (76%) reported implementing DSD. Of these, 91% offered DSD for HIV treatment, 61% for HIV testing and 59% for antiretroviral therapy (ART) initiation. The most common duration of ART refills for clinically stable clients was 3MMD, (70%), followed by monthly (14%) and 6MMD (10%). Facility-based individual models were the most frequently available DSD for the HIV treatment model (82%), followed by client-managed group models (60%). Out-of-facility individual models were available at 48% of facilities. Facility-based individual models were particularly common among facilities in East (92%) and Southern Africa (96%). Facilities in medium and high HIV prevalence countries, and those with 3MMD, were more likely to implement DSD. CONCLUSIONS: In 2019, DSD was available in most HIV care facilities globally but was not evenly implemented across regions and HIV services. Most offered facility-based DSD for HIV treatment models and 3MMD for clinically stable clients. Efforts to expand DSD for HIV testing and ART initiation and to offer longer MMD can improve long-term retention in care of people living with HIV in LMICs, while further alleviating the operational burden on healthcare services. These findings from the pre-COVID-19 era underline the need for strengthening DSD in HIV care, which remains at the centre of current efforts towards client-centred care.
The impact of the SKILLZ intervention on sexual and reproductive health empowerment among Zambian adolescent girls and young women: results of a cluster randomized controlled trial.
(2025-Jun-05) Sheira LA; Mulubwa C; Chiu C; Chipungu J; Coakley C; Smith H; Upadhyay UD; Chilambe C; Chibwe B; Pry JM; Mkandawire B; Musonda M; Moore CB; Liu J
BACKGROUND: Zambian adolescent girls and young women (AGYW, age 15–24) experience a disproportionate burden of HIV and unintended pregnancy. Sports-based interventions, which affect sexual health behaviors via improving sexual and reproductive empowerment, may be an innovative and effective approach for promoting HIV and unintended pregnancy prevention. We sought to evaluate the impact of a peer-led, sports-based intervention on sexual and reproductive empowerment among in-school Zambian adolescent girls and young women. METHODS: Data come from the ‘SKILLZ’ study, a cluster randomized controlled trial evaluating the impact of a peer-led, sports-based health education program. Sexual and reproductive empowerment, a secondary outcome of SKILLZ, was measured via the 23-item Sexual and Reproductive Empowerment for adolescents and young adults scale (range 0–92, higher = more sexual and reproductive empowerment) three times over approximately 24 months. We conducted a difference-in-differences analysis to evaluate intervention impact over time. RESULTS: The study enrolled 2,153 AGYW (1134 intervention; 1019 control) across 46 secondary schools in Lusaka. Median age at baseline was 17; participants were largely unmarried (96%), with 20% reporting any sexual activity. By endline, nearly 40% reported being sexually active. Between baseline and midline, attending an intervention school was associated with a 6.21-point increase in overall score calculated using the imputed sample (standard error [SE]: 0.75, CONCLUSION: The intervention moderately impacted Sexual and Reproductive Empowerment scores; results were magnified among sexually active AGYW. Given adolescence is a critical period for sexuality and gender programming, as well as for sexual debut, empowerment interventions at schools may support downstream sexual health behaviors that will impact the life-course of AGYW. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (NCT04429061) on March 17th, 2020. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12978-025-02046-6.