Browsing by Author "Bolton-Moore, Carolyn"

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A Review of Differentiated Service Delivery for HIV Treatment: Effectiveness, Mechanisms, Targeting, and Scale.
(2019-Aug) Roy, Monika; Bolton-Moore, Carolyn; Sikazwe, Izukanji; Holmes, Charles B.
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.
Accurate dried blood spots collection in the community using non-medically trained personnel could support scaling up routine viral load testing in resource limited settings.
(2019) Sikombe, Kombatende; Hantuba, Cardinal; Musukuma, Kalo; Sharma, Anjali; Padian, Nancy; Holmes, Charles; Czaicki, Nancy; Simbeza, Sandra; Somwe, Paul; Bolton-Moore, Carolyn; Sikazwe, Izukanji; Geng, Elvin
Regular plasma HIV-RNA testing for persons living with HIV on antiretroviral therapy (ART) is now the global standard, but as many as 60% of persons in Africa today on ART do not have access to standard laboratory HIV-RNA assays. As a result, patients in Zambia often receive treatment without any means of determining true virologic failure, which poses a risk of premature switch of ART regimens and widespread HIV drug resistance. Dry blood spots (DBS) on the other hand require unskilled personnel and less complex storage supply chain so are ideal to capture viral-load results from HIV patients outside clinic settings. We assess collection of DBS in the community using non-medically trained personnel (NMP) and documented challenges. We trained 23 NMP to collect DBS from lost to follow-up (LTFU) patients in 4 rural and urban Zambian districts. We developed a phlebotomy box to transport DBS without contamination at ambient temperature and concomitant training and standard operating procedures. We evaluated this through field observations, bi-weekly meetings, reports, and staff meetings. The laboratory assessed DBS quality for testing validity. We attempted to collect DBS from 357 participants in the community. Though individual reasons for refusal from the remaining 37% were not collected, NMPs reported privacy concerns, awkward box-size which drew attention in the community and fears of undisclosed uses of samples related to witchcraft and circulating narratives about past research. Successful DBS collection was not associated with patient gender, age, time on ART, enrolment CD4, facility. DBS viral-load collection by NMP is feasible in Zambia. Our training approach and assessments of NMP not part of the health system can be extended to patients by giving them more responsibility to manage their own differentiated care groups. Concerted efforts that compare collection of DBS by NMP to those collected by skilled-medical personnel are needed.
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, Monika; Holmes, Charles; Sikazwe, Izukanji; Savory, Thea; wa Mwanza, Mwanza; Bolton-Moore, Carolyn; Mulenga, Kafula; Czaicki, Nancy; Glidden, David V.; Padian, Nancy; Geng, Elvin
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.
Association of Virologic Failure and Nonnucleoside Reverse Transcriptase Inhibitor Resistance Found in Antiretroviral-Naive Children Infected With Human Immunodeficiency Virus and Given Efavirenz-Based Treatment.
(2020-Apr-30) Higa, Nikki; Pelz, Amy; Birch, Donald; Beck, Ingrid A.; Sils, Tatiana; Samson, Pearl; Bwakura-Dangarembizi, Mutsawashe; Bolton-Moore, Carolyn; Capparelli, Edmund; Chadwick, Ellen; Frenkel, Lisa M.
Among 66 antiretroviral-naive children aged <3 years with human immunodeficiency virus (HIV) or coinfected with HIV and tuberculosis and initiating efavirenz-based antiretroviral therapy (ART), non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was detected before ART in 5 (7.6%). Virologic failure occurred in 2 of these children; they were last tested at 16 and 24 weeks of ART. Pre-ART NNRTI resistance was not associated with virologic failure.
Barriers to HIV care and adherence for young people living with HIV in Zambia and mHealth.
(2019) St Clair-Sullivan, Natalie; Mwamba, Chanda; Whetham, Jennifer; Bolton-Moore, Carolyn; Darking, Mary; Vera, Jaime
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.
Causes of morbidity among HIV-infected children on antiretroviral therapy in primary care facilities in Lusaka, Zambia.
(2009-Oct) Mubiana-Mbewe, Mwangelwa; Bolton-Moore, Carolyn; Banda, Yolan; Chintu, Namwinga; Nalubamba-Phiri, Mutinta; Giganti, Mark; Guffey, Brad M.; Sambo, Pauline; Stringer, Elizabeth M.; Stringer, Jeffrey S.; Chi, Benjamin H.
OBJECTIVES: To describe the pattern of incident illness in children after initiation of antiretroviral therapy (ART) in a large public health sector programme in Lusaka, Zambia. METHODS: Systematic chart review to retrospectively extract data from medical records of children (i.e. <15 years) initiating ART in the Lusaka, Zambia public sector. Incident conditions were listed separately and then grouped according to broad categories. Predictors for incident diagnoses were determined using univariate and multivariable analysis. RESULTS: Between May 2004 and June 2006, 1705 HIV-infected children initiated ART. Of these, 1235 (72%) had their medical records reviewed. Median age at ART initiation was 77 months and 554 (45%) were females. Eight hundred and forty-one (68%) children had an incident condition during this period, with a median time of occurrence of 64 days from ART initiation. Twenty-eight incident conditions were documented. When categorized, the most common were mucocutaneous conditions [incidence rate (IR): 70.6 per 100 child-years, 95% CI: 64.5-77.2] and upper respiratory tract infection (IR: 70.1 per 100 child-years; 95% CI: 64.0-76.7). Children with severe immunosuppression (i.e. CD4 < 10%) were more likely to develop lower respiratory tract infection (16.3%vs. 10.2%; P = 0.003) and mucocutaneous conditions (43.9% vs. 35.3%; P = 0.005) than those with CD4 > or = 10%. CONCLUSION: There is a high incidence of new illness after ART initiation, emphasizing the importance of close monitoring during this period. Early initiation of ART and use of antimicrobial prophylaxis may also help to reduce the occurrence of such co-morbidities.
Causes of stillbirth, neonatal death and early childhood death in rural Zambia by verbal autopsy assessments.
(2011-Jul) Turnbull, Eleanor; Lembalemba, Mwila K.; Guffey, Brad M.; Bolton-Moore, Carolyn; Mubiana-Mbewe, Mwangelwa; Chintu, Namwinga; Giganti, Mark J.; Nalubamba-Phiri, Mutinta; Stringer, Elizabeth M.; Stringer, Jeffrey S.; Chi, Benjamin H.
OBJECTIVES: To describe specific causes of the high rates of stillbirth, neonatal death and early child childhood death in Zambia. METHODS: We conducted a household-based survey in rural Zambia. Socio-demographic and delivery characteristics were recorded, alongside a maternal HIV test. Verbal autopsy questionnaires were administered to elicit mortality-related information and independently reviewed by three experienced paediatricians who assigned a cause and contributing factor to death. For this secondary analysis, deaths were categorized into: stillbirths (foetal death ≥28 weeks of gestation), neonatal deaths (≤28 days) and early childhood deaths (>28 days to <2 years). RESULTS: Among 1679 households, information was collected on 148 deaths: 34% stillbirths, 26% neonatal and 40% early childhood deaths. Leading identifiable causes of stillbirth were intrauterine infection (26%) and birth asphyxia (18%). Of 32 neonatal deaths, 38 (84%) occurred within the first week of life, primarily because of infections (37%) and prematurity (34%). The majority of early childhood deaths were caused by suspected bacterial infections (82%). HIV prevalence was significantly higher in mothers who reported an early childhood death (44%) than mothers who did not (17%; P < 0.01). Factors significantly associated with mortality were lower socio-economic status (P < 0.01), inadequate water or sanitation facilities (P < 0.01), home delivery (P = 0.04) and absence of a trained delivery attendant (P < 0.01). CONCLUSION: We provide community-level data about the causes of death among children under 2 years of age. Infectious etiologies for mortality ranked highest. At a public health level, such information may have an important role in guiding prevention and treatment strategies to address perinatal and early childhood mortality.
Characteristics and outcomes of adolescents living with perinatally acquired HIV within Southern Africa.
(2020-Dec-01) Tsondai, Priscilla R.; Braithwaite, Kate; Fatti, Geoffrey; Bolton-Moore, Carolyn; Chimbetete, Cleophas ; Rabie, Helena; Phiri, Sam; Sawry, Shobna ; Eley, Brian; Hobbins, Michael A.; Boulle, Andrew; Taghavi, Katayoun; Sohn, Annette H.; Davies, Mary-Ann
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.
Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia.
(2007-Oct-24) Bolton-Moore, Carolyn; Mubiana-Mbewe, Mwangelwa; Cantrell, Ronald A.; Chintu, Namwinga; Stringer, Elizabeth M.; Chi, Benjamin H.; Sinkala, Moses; Kankasa, Chipepo; Wilson, Craig M.; Wilfert, Catherine M.; Mwango, Albert; Levy, Jens; Abrams, Elaine J.; Bulterys, Marc; Stringer, Jeffrey S.
CONTEXT: The Zambian Ministry of Health provides pediatric antiretroviral therapy (ART) at primary care clinics in Lusaka, where, despite scale-up of perinatal prevention efforts, many children are already infected with the human immunodeficiency virus (HIV). OBJECTIVE: To report early clinical and immunologic outcomes of children enrolled in the pediatric treatment program. DESIGN, SETTING, AND PATIENTS: Open cohort assessment using routinely collected clinical and outcome data from an electronic medical record system in use at 18 government primary health facilities in Lusaka, Zambia. Care was provided primarily by nurses and clinical officers ("physician extenders" akin to physician assistants in the United States). Patients were children (<16 years of age) presenting for HIV care between May 1, 2004, and June 29, 2007. INTERVENTION: Three-drug ART (zidovudine or stavudine plus lamivudine plus nevirapine or efavirenz) for children who met national treatment criteria. MAIN OUTCOME MEASURES: Survival, weight gain, CD4 cell count, and hemoglobin response. RESULTS: After enrollment of 4975 children into HIV care, 2938 (59.1%) started ART. Of those initiating ART, the median age was 81 months (interquartile range, 36-125), 1531 (52.1%) were female, and 2087 (72.4%) with World Health Organization stage information were in stage III or IV. At the time of analysis, 158 children (5.4%) had withdrawn from care and 382 (13.0%) were at least 30 days late for follow-up. Of the remaining 2398 children receiving ART, 198 (8.3%) died over 3018 child-years of follow-up (mortality rate, 6.6 deaths per 100 child-years; 95% confidence interval [CI], 5.7-7.5); of these deaths, 112 (56.6%) occurred within 90 days of therapy initiation (early mortality rate, 17.4/100 child-years; post-90-day mortality rate, 2.9/100 child-years). Mortality was associated with CD4 cell depletion, lower weight-for-age, younger age, and anemia in multivariate analysis. The mean CD4 cell percentage at ART initiation among the 1561 children who had at least 1 repeat measurement was 12.9% (95% CI, 12.5%-13.3%) and increased to 23.7% (95% CI, 23.1%-24.3%) at 6 months, 27.0% (95% CI, 26.3%-27.6%) at 12 months, 28.0% (95% CI, 27.2%-28.8%) at 18 months, and 28.4% (95% CI, 27.4%-29.4%) at 24 months. CONCLUSIONS: Care provided by clinicians such as nurses and clinical officers can result in good outcomes for HIV-infected children in primary health care settings in sub-Saharan Africa. Mortality during the first 90 days of therapy is high, pointing to a need for earlier intervention.
Cohort profile: Noncommunicable diseases and ideal cardiovascular health among people living with and without HIV in Zambia and Zimbabwe (NCDzz cohort).
(2025-Feb-07) Chihota, Belinda V.; Mandiriri, Ardele; Muula, Guy; Banda, Esau; Shamu, Tinei; Bolton-Moore, Carolyn; Chimbetete, Cleophas; Bosomprah, Samuel; Wandeler, Gilles
PURPOSE: The NCDzz study is a prospective cohort of people living with and without HIV attending primary care clinics in Zambia and Zimbabwe and was established in 2019 to understand the intersection between noncommunicable diseases (NCDs) and HIV in Southern Africa. Here, we describe the study design and population and evaluate their ideal cardiovascular health (ICVH) using the Life's Simple 7 (LS7) score according to the American Heart Association. PARTICIPANTS: Antiretroviral therapy-naïve people living with HIV (PLWH) and people living without HIV (PLWOH) 30 years or older were recruited from three primary care clinics in Lusaka and Harare, and underwent comprehensive clinical, laboratory and behavioural assessments. All study measurements are repeated during yearly follow-up visits. PLWOH were recruited from the same neighbourhoods and had similar socioeconomic conditions as PLWH. FINDINGS TO DATE: Between August 2019 and March 2023, we included 1100 adults, of whom 618 (56%) were females and 539 (49%) were PLWH. The median age at enrolment was 39 years (IQR 34-46 years). Among 1013 participants (92%) with complete data, the median LS7 score was 11/14 (IQR 10-12). Overall, 60% of participants met the criteria of ICVH metrics (5-7 ideal components) and among individual components of the LS7, more females had poor body mass index (BMI) than males, regardless of HIV status (27% vs 3%, p<0.001). Our data show no apparent difference in cardiovascular health determinants between men and women, but high BMI in women and overall high hypertension prevalence need detailed investigation. Untreated HIV (OR: 1.36 (IQR 1.05-1.78)) and being a Zambian participant (OR: 1.81 (IQR 1.31-2.51)) were associated with having ICVH metrics, whereas age older than 50 years (OR: 0.46 (IQR 0.32-0.65)) was associated with not having ICVH metrics. FUTURE PLANS: Our study will be regularly updated with upcoming analyses using prospective data including a focus on arterial hypertension and vascular function. We plan to enrich the work through conducting in-depth assessments on the determinants of cardiovascular, liver and kidney end-organ disease outcomes yearly. Additionally, we seek to pilot NCD interventions using novel methodologies like the trials within cohorts. Beyond the initial funding support, we aim to collect at minimum yearly data for an additional 5-year period.
Comparative outcomes of tenofovir-based and zidovudine-based antiretroviral therapy regimens in Lusaka, Zambia.
(2011-Dec-15) Chi, Benjamin H.; Mwango, Albert; Giganti, Mark J.; Sikazwe, Izukanji ; Moyo, Crispin; Schuttner, Linnaea; Mulenga, Lloyd B.; Bolton-Moore, Carolyn; Chintu, Namwinga T.; Sheneberger, Robert; Stringer, Elizabeth M.; Stringer, Jeffrey S.
BACKGROUND: Although tenofovir (TDF) is a common component of antiretroviral therapy (ART), recent evidence suggests inferior outcomes when it is combined with nevirapine (NVP). METHODS: We compared outcomes among patients initiating TDF + emtricitabine or lamivudine (XTC) + NVP, TDF + XTC + efavirenz (EFV), zidovudine (ZDV) + lamuvidine (3TC) + NVP, and ZDV + 3TC + EFV. We categorized drug exposure by initial ART dispensation by a time-varying analysis that accounted for drug substitutions and by predominant exposure (>75% of drug dispensations) during an initial window period. Risks for death and program failure were estimated using Cox proportional hazard models. All regimens were compared with ZDV + 3TC + NVP. RESULTS: Between July 2007 and November 2010, 18,866 treatment-naive adults initiated ART: 18.2% on ZDV + 3TC + NVP, 1.8% on ZDV + 3TC + EFV, 36.2% on TDF + XTC + NVP, and 43.8% on TDF + XTC + EFV. When exposure was categorized by initial prescription, patients on TDF + XTC + NVP [adjusted hazard ratio (AHR): 1.45; 95% confidence interval (CI): 1.03 to 2.06] had a higher post-90-day mortality. TDF + XTC + NVP was also associated with an elevated risk for mortality when exposure was categorized as time-varying (AHR: 1.51; 95% CI: 1.18 to 1.95) or by predominant exposure over the first 90 days (AHR: 1.91, 95% CI: 1.09 to 3.34). However, these findings were not consistently observed across sensitivity analyses or when program failure was used as a secondary outcome. CONCLUSION: TDF + XTC + NVP was associated with higher mortality when compared with ZDV + 3TC + NVP but not consistently across sensitivity analyses. These findings may be explained in part by inherent limitations to our retrospective approach, including residual confounding. Further research is urgently needed to compare the effectiveness of ART regimens in use in resource-constrained settings.
Contraceptive use among HIV-infected women and men receiving antiretroviral therapy in Lusaka, Zambia: a cross-sectional survey.
(2016-May-12) Hancock, Nancy L.; Chibwesha, Carla J.; Bosomprah, Samuel; Newman, Jonathan; Mubiana-Mbewe, Mwangelwa ; Sitali, Elizabeth S.; Bolton-Moore, Carolyn; Mbwili-Muleya, Clara; Chi, Benjamin H.
BACKGROUND: Family planning (FP) is an essential health service and an important part of comprehensive HIV care. However, there is limited information about the contraceptive needs of people living with HIV in sub-Saharan Africa, which in turn has hampered efforts to expand and integrate FP services into existing HIV programs. METHODS: We performed a cross-sectional survey to determine FP prevalence and predictors among HIV-positive women and men attending 18 public antiretroviral therapy (ART) clinics in Lusaka, Zambia. Trained peer counselors administered the 10-question survey to those seeking care for five days at each of the target sites. RESULTS: From February to April 2014, we surveyed 7,046 HIV-infected patients receiving routine HIV services. Use of modern contraception was reported by 69 % of female ART patients and 79 % of male ART patients. However, highly effective contraceptive use and dual method use were low among women (38 and 25 %, respectively) and men (19 and 14 %, respectively). HIV disclosure status (adjusted odds ratio (AOR) = 4.91, 95 % confidence interval (CI) = 3.32-7.24 for women, AOR = 3.58, 95 % CI = 2.39-5.38 for men) and sexual activity in the last 6 months (AOR = 5.80, 95 % CI = 4.51-7.47 for women, AOR = 6.24, 95 % CI = 3.51-11.08 for men) were associated with modern contraceptive use in multivariable regression. Most respondents said they would access FP services if made available within ART clinic. CONCLUSIONS: While FP-ART integration may be a promising strategy for increasing FP service uptake, such services must focus on assessing sexual activity and advocating for dual method use to increase effective contraceptive use and prevent unintended pregnancies.
Differentiated Care Preferences of Stable Patients on Antiretroviral Therapy in Zambia: A Discrete Choice Experiment.
(2019-Aug-15) Eshun-Wilson, Ingrid; Mukumbwa-Mwenechanya, Mpande; Kim, Hae-Young; Zannolini, Arianna; Mwamba, Chanda P.; Dowdy, David; Kalunkumya, Estella; Lumpa, Mwansa; Beres, Laura K.; Roy, Monika; Sharma, Anjali; Topp, Stephanie M.; Glidden, Dave V.; Padian, Nancy; Ehrenkranz, Peter; Sikazwe, Izukanji; Holmes, Charles B.; Bolton-Moore, Carolyn; Geng, Elvin H.
BACKGROUND: Although differentiated service delivery (DSD) models for stable patients on antiretroviral therapy (ART) offer a range of health systems innovations, their comparative desirability to patients remains unknown. We conducted a discrete choice experiment to quantify service attributes most desired by patients to inform model prioritization. METHODS: Between July and December 2016, a sample of HIV-positive adults on ART at 12 clinics in Zambia were asked to choose between 2 hypothetical facilities that differed across 6 DSD attributes. We used mixed logit models to explore preferences, heterogeneity, and trade-offs. RESULTS: Of 486 respondents, 59% were female and 85% resided in urban locations. Patients strongly preferred infrequent clinic visits [3- vs. 1-month visits: β (ie, relative utility) = 2.84; P < 0.001]. Milder preferences were observed for waiting time for ART pick-up (1 vs. 6 hours.; β = -0.67; P < 0.001) or provider (1 vs. 3 hours.; β = -0.41; P = 0.002); "buddy" ART collection (β = 0.84; P < 0.001); and ART pick-up location (clinic vs. community: β = 0.35; P = 0.028). Urban patients demonstrated a preference for collecting ART at a clinic (β = 1.32, P < 0.001), and although most rural patients preferred community ART pick-up (β = -0.74, P = 0.049), 40% of rural patients still preferred facility ART collection. CONCLUSIONS: Stable patients on ART primarily want to attend clinic infrequently, supporting a focus in Zambia on optimizing multimonth prescribing over other DSD features-particularly in urban areas. Substantial preference heterogeneity highlights the need for DSD models to be flexible, and accommodate both setting features and patient choice in their design.
Does provider-initiated counselling and testing (PITC) strengthen early diagnosis and treatment initiation? Results from an analysis of an urban cohort of HIV-positive patients in Lusaka, Zambia.
(2012-Sep-24) Topp, Stephanie M.; Li, Michelle S.; Chipukuma, Julien M.; Chiko, Matimba M.; Matongo, Evelyn; Bolton-Moore, Carolyn; Reid, Stewart E.
INTRODUCTION: Building on earlier works demonstrating the effectiveness and acceptability of provider-initiated counselling and testing (PITC) services in integrated outpatient departments of urban primary healthcare clinics (PHCs), this study seeks to understand the relative utility of PITC services for identifying clients with early-stage HIV-related disease compared to traditional voluntary testing and counselling (VCT) services. We additionally seek to determine whether there are any significant differences in the clinical and demographic profile of PITC and VCT clients. METHODS: Routinely collected, de-identified data were collated from two cohorts of HIV-positive patients referred for HIV treatment, either from PITC or VCT in seven urban-integrated PHCs. Univariate and multivariate analyses were conducted to compare the two cohorts across demographic and clinical characteristics at enrolment. RESULTS: Forty-five per cent of clients diagnosed via PITC had CD4 < 200, and more than 70% (i.e. two thirds) had CD4 < 350 at enrollment, with significantly lower CD4 counts than that of VCT clients (p < 0.001). PITC clients were more likely to be male (p = 0.0005) and less likely to have secondary or tertiary education (p < 0.0001). Among those who were initiated on antiretroviral therapy (ART), PITC clients had lower odds of initiating treatment within four weeks of enrollment into HIV care (adjusted odds ratio, or AOR: 0.86; 95% confidence interval, or CI: 0.75-0.99; p = 0.035) and significantly lower odds of retention in care at six months (AOR: 0.84; CI: 0.77-0.99; p = 0.004). CONCLUSIONS: In Lusaka, Zambia, large numbers of individuals with late-stage HIV are being incidentally diagnosed in outpatient settings. Our findings suggest that PITC in this setting does not facilitate more timely diagnosis and referral to care but rather act as a "safety net" for individuals who are unwilling or unable to seek testing independently. Further work is needed to document the way provision of clinic-based services can be strengthened and linked to community-based interventions and to address socio-cultural norms and socio-economic status that underpin healthcare-seeking behaviour.
Drug Resistance in People With Viremia on Dolutegravir-based Antiretroviral Therapy in Sub-Saharan Africa: The DTG RESIST Study.
(2025-May-20) Loosli, Tom; Bolton-Moore, Carolyn; Buzaalirwa, Lydia; Byakwaga, Helen; Çelikağ, İpek; Chimbetete, Cleophas; Ebasone, Peter V.; Giandhari, Jennifer; Han, Nuri; Huwa, Jacqueline; Kasozi, Charles; Mafoua, Adolphe; Messou, Eugène ; Minga, Albert; Muula, Guy; Muyindike, Winnie; Ndala, Arcel C. M.; Sauermann, Mamatha ; Semeere, Aggrey; Singh, Lavanya; Kouyos, Roger D.; Lessells, Richard; Egger, Matthias
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.
Early clinical and programmatic outcomes with tenofovir-based antiretroviral therapy in Zambia.
(2010-May-01) Chi, Benjamin H.; Mwango, Albert; Giganti, Mark; Mulenga, Lloyd B.; Tambatamba-Chapula, Bushimbwa ; Reid, Stewart E.; Bolton-Moore, Carolyn; Chintu, Namwinga ; Mulenga, Priscilla L.; Stringer, Elizabeth M.; Sheneberger, Robert; Mwaba, Peter; Stringer, Jeffrey S.
BACKGROUND: In July 2007, amid some controversy over cost, Zambia was the first African country to introduce tenofovir (TDF) as a component of first-line antiretroviral therapy (ART) on a wide scale. METHODS: We compared drug substitutions, mortality, and "programmatic failure" among adults starting TDF-, zidovudine (ZDV)-, and stavudine (d4T)-containing ART. Programmatic failure was defined as death, withdrawal, or loss to follow-up. RESULTS: Between July 2007 and January 2009, 10,485 adults initiated ART (66% on TDF, 23% on ZDV, 11% on d4T), with a median follow-up time of 239 (interquartile range 98, 385) days. Those starting TDF were more likely to be male and more likely to have indicators of severe disease at baseline. In adjusted Cox proportional hazards models, ZDV- (adjusted hazard ratio [AHR] = 2.74, 95% confidence interval [CI] = 2.30-3.28) and d4T-based regimens (AHR = 1.92, 95% CI = 1.55-2.38) were associated with higher risk for drug substitution when compared with TDF-based regimens. Similar hazards were noted for overall mortality (ZDV: AHR = 0 .81, 95% CI = 0.62-1.06; d4T: AHR = 1.03, 95% CI = 0.74-1.43) and programmatic failure (ZDV: AHR = 0.99, 95% CI = 0.88-1.11; d4T: AHR = 1.11, 95% CI = 0.96-1.28) when compared with TDF. CONCLUSIONS: TDF is associated with similar clinical and programmatic outcomes as ZDV and d4T but appears to be better tolerated. Although further evaluation is needed, these results are encouraging and support Zambia's policy decision.
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, Kombatende; Mody, Aaloke; Goss, Charles W.; Simbeza, Sandra; Beres, Laura K.; Pry, Jake M.; Eshun-Wilson, Ingrid; Sharma, Anjali; Mukamba, Njekwa; Mulenga, Lloyd B.; Rice, Brian; Mutale, Jacob; Zulu, Alida D.; Mulabe, Musunge; Hargreaves, James; Bolton-Moore, Carolyn; Holmes, Charles B.; Sikazwe, Izukanji ; Geng, Elvin H.
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.
Establishing Dosing Recommendations for Efavirenz in HIV/TB-Coinfected Children Younger Than 3 Years.
(2019-Aug-01) Dangarembizi, Mutsa B.; Samson, Pearl; Capparelli, Edmund V.; Bolton-Moore, Carolyn; Jean-Philippe, Patrick; Spector, Stephen A.; Chakhtoura, Nahida; Benns, Alex; Zimmer, Bonnie; Purdue, Lynette; Jackson, Chivon; Wallis, Carole; Libous, Jennifer L.; Chadwick, Ellen G.
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.
Estimated mortality on HIV treatment among active patients and patients lost to follow-up in 4 provinces of Zambia: Findings from a multistage sampling-based survey.
(2018-Jan) Holmes, Charles B.; Sikazwe, Izukanji; Sikombe, Kombatende; Eshun-Wilson, Ingrid; Czaicki, Nancy; Beres, Laura K.; Mukamba, Njekwa; Simbeza, Sandra; Bolton-Moore, Carolyn; Hantuba, Cardinal; Mwaba, Peter; Phiri, Caroline; Padian, Nancy; Glidden, David V.; Geng, Elvin
BACKGROUND: Survival represents the single most important indicator of successful HIV treatment. Routine monitoring fails to capture most deaths. As a result, both regional assessments of the impact of HIV services and identification of hotspots for improvement efforts are limited. We sought to assess true mortality on treatment, characterize the extent under-reporting of mortality in routine health information systems in Zambia, and identify drivers of mortality across sites and over time using a multistage, regionally representative sampling approach. METHODS AND FINDINGS: We enumerated all HIV infected adults on antiretroviral therapy (ART) who visited any one of 64 facilities across 4 provinces in Zambia during the 24-month period from 1 August 2013 to 31 July 2015. We identified a probability sample of patients who were lost to follow-up through selecting facilities probability proportional to size and then a simple random sample of lost patients. Outcomes among patients lost to follow-up were incorporated into survival analysis and multivariate regression through probability weights. Of 165,464 individuals (64% female, median age 39 years (IQR 33-46), median CD4 201 cells/mm3 (IQR 111-312), the 2-year cumulative incidence of mortality increased from 1.9% (95% CI 1.7%-2.0%) to a corrected rate of 7.0% (95% CI 5.7%-8.4%) (all ART users) and from 2.1% (95% CI 1.8%-2.4%) to 8.3% (95% CI 6.1%-10.7%) (new ART users). Revised provincial mortality rates ranged from 3-9 times higher than naïve rates for new ART users and were lowest in Lusaka Province (4.6 per 100 person-years) and highest in Western Province (8.7 per 100 person-years) after correction. Corrected mortality rates varied markedly by clinic, with an IQR of 3.5 to 7.5 deaths per 100 person-years and a high of 13.4 deaths per 100 person-years among new ART users, even after adjustment for clinical (e.g., pretherapy CD4) and contextual (e.g., province and clinic size) factors. Mortality rates (all ART users) were highest year 1 after treatment at 4.6/100 person-years (95% CI 3.9-5.5), 2.9/100 person-years (95% CI 2.1-3.9) in year 2, and approximately 1.6% per year through 8 years on treatment. In multivariate analysis, patient-level factors including male sex and pretherapy CD4 levels and WHO stage were associated with higher mortality among new ART users, while male sex and HIV disclosure were associated with mortality among all ART users. In both cases, being late (>14 days late for appointment) or lost (>90 days late for an appointment) was associated with deaths. We were unable to ascertain the vital status of about one-quarter of those lost and selected for tracing and did not adjudicate causes of death. CONCLUSIONS: HIV treatment in Zambia is not optimally effective. The high and sustained mortality rates and marked under-reporting of mortality at the provincial-level and unexplained heterogeneity between regions and sites suggest opportunities for the use of corrected mortality rates for quality improvement. A regionally representative sampling-based approach can bring gaps and opportunities for programs into clear epidemiological focus for local and global decision makers.
Estimating the real-world effects of expanding antiretroviral treatment eligibility: Evidence from a regression discontinuity analysis in Zambia.
(2018-Jun) Mody, Aaloke; Sikazwe, Izukanji; Czaicki, Nancy L.; Wa Mwanza, Mwanza; Savory, Theodora; Sikombe, Kombatende; Beres, Laura K.; Somwe, Paul; Roy, Monika; Pry, Jake M.; Padian, Nancy; Bolton-Moore, Carolyn; Holmes, Charles B.; Geng, Elvin H.
BACKGROUND: Although randomized trials have established the clinical efficacy of treating all persons living with HIV (PLWHs), expanding treatment eligibility in the real world may have additional behavioral effects (e.g., changes in retention) or lead to unintended consequences (e.g., crowding out sicker patients owing to increased patient volume). Using a regression discontinuity design, we sought to assess the effects of a previous change to Zambia's HIV treatment guidelines increasing the threshold for treatment eligibility from 350 to 500 cells/μL to anticipate effects of current global efforts to treat all PLWHs. METHODS AND FINDINGS: We analyzed antiretroviral therapy (ART)-naïve adults who newly enrolled in HIV care in a network of 64 clinics operated by the Zambian Ministry of Health and supported by the Centre for Infectious Disease Research in Zambia (CIDRZ). Patients were restricted to those enrolling in a narrow window around the April 1, 2014 change to Zambian HIV treatment guidelines that raised the CD4 threshold for treatment from 350 to 500 cells/μL (i.e., August 1, 2013, to November 1, 2014). Clinical and sociodemographic data were obtained from an electronic medical record system used in routine care. We used a regression discontinuity design to estimate the effects of this change in treatment eligibility on ART initiation within 3 months of enrollment, retention in care at 6 months (defined as clinic attendance between 3 and 9 months after enrollment), and a composite of both ART initiation by 3 months and retention in care at 6 months in all new enrollees. We also performed an instrumental variable (IV) analysis to quantify the effect of actually initiating ART because of this guideline change on retention. Overall, 34,857 ART-naïve patients (39.1% male, median age 34 years [IQR 28-41], median CD4 268 cells/μL [IQR 134-430]) newly enrolled in HIV care during this period; 23,036 were analyzed after excluding patients around the threshold to allow for clinic-to-clinic variations in actual guideline uptake. In all newly enrolling patients, expanding the CD4 threshold for treatment from 350 to 500 cells/μL was associated with a 13.6% absolute increase in ART initiation within 3 months of enrollment (95% CI, 11.1%-16.2%), a 4.1% absolute increase in retention at 6 months (95% CI, 1.6%-6.7%), and a 10.8% absolute increase in the percentage of patients who initiated ART by 3 months and were retained at six months (95% CI, 8.1%-13.5%). These effects were greatest in patients who would have become newly eligible for ART with the change in guidelines: a 43.7% increase in ART initiation by 3 months (95% CI, 37.5%-49.9%), 13.6% increase in retention at six months (95% CI, 7.3%-20.0%), and a 35.5% increase in the percentage of patients on ART at 3 months and still in care at 6 months [95% CI, 29.2%-41.9%). We did not observe decreases in ART initiation or retention in patients not directly targeted by the guideline change. An IV analysis found that initiating ART in response to the guideline change led to a 37.9% (95% CI, 28.8%-46.9%) absolute increase in retention in care. Limitations of this study include uncertain generalizability under newer models of care, lack of laboratory data (e.g., viral load), inability to account for earlier stages in the HIV care cascade (e.g., HIV testing and linkage), and potential for misclassification of eligibility status or outcome. CONCLUSIONS: In this study, guidelines raising the CD4 threshold for treatment from 350 to 500 cells/μL were associated with a rapid rise in ART initiation as well as enhanced retention among newly treatment-eligible patients, without negatively impacting patients with lower CD4 levels. These data suggest that health systems in Zambia and other high-prevalence settings could substantially enhance engagement even among those with high CD4 levels (i.e., above 500 cells/μL) by expanding treatment without undermining existing care standards.