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The CIDRZ Research Repository serves as an open-access archive for peer-reviewed publications, conference papers, and other scholarly outputs from CIDRZ researchers. Our goal is to promote the dissemination of knowledge and support evidence-based public health initiatives.
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Item 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 At the time of analysis, 158 children (5.4%) had withdrawn from care and 382 (13.0%) were at least 30 days late for follow-up.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.Item 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.Item 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.Item 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.Item 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.Item Opt-out provider-initiated HIV testing and counselling in primary care outpatient clinics in Zambia.(2011-May-01) Topp, Stephanie M.; Chipukuma, Julien M.; Chiko, Matimba M.; Wamulume, Chibesa S.; Bolton-Moore, Carolyn; Reid, Stewart E.OBJECTIVE: To increase case-finding of infection with human immunodeficiency virus (HIV) in Zambia and their referral to HIV care and treatment by supplementing existing client-initiated voluntary counselling and testing (VCT), the dominant mode of HIV testing in the country. METHODS: Lay counsellors offered provider-initiated HIV testing and counselling (PITC) to all outpatients who attended primary clinics and did not know their HIV serostatus. Data on counselling and testing were collected in registers. Outcomes of interest included HIV testing coverage, the acceptability of testing, the proportion testing HIV-positive (HIV+), the proportion enrolling in HIV care and treatment and the time between testing and enrolment. FINDINGS: After the addition of PITC to VCT, the number tested for HIV infection in the nine clinics was twice the number undergoing VCT alone. Over 30 months, 44,420 patients were counselled under PITC and 31,197 patients, 44% of them men, accepted testing. Of those tested, 21% (6572) were HIV+; 38% of these HIV+ patients (2515) enrolled in HIV care and treatment. The median time between testing and enrolment was 6 days. The acceptability of testing rose over time. CONCLUSION: The introduction of routine PITC using lay counsellors into health-care clinics in Lusaka, Zambia, dramatically increased the uptake and acceptability of HIV testing. Moreover, PITC was incorporated rapidly into primary care outpatient departments. Maximizing the number of patients who proceed to HIV care and treatment remains a challenge and warrants further research.Item 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.Item Evaluation of a Task-Shifting Strategy Involving Peer Educators in HIV Care and Treatment Clinics in Lusaka, Zambia.(2012-Mar-07) Born, Lonny J.; Wamulume, Chibesa; Neroda, Kim A.; Quiterio, Nicole; Giganti, Mark J.; Morris, Mary; Bolton-Moore, Carolyn; Baird, Shelagh; Sinkamba, Maggie; Topp, Stephanie M.; Reid, Stewart E.Rapid expansion of antiretroviral therapy (ART) and a shortage of health care workers (HCWs) required the implementation of a peer educator (PE) model as part of a task-shifting strategy in Lusaka District clinics. The purpose of this study was to evaluate patient and staff perceptions regarding whether the PE program: a) relieved the workload on professional HCWs; and b) delivered services of acceptable quality. Qualitative and quantitative data were gathered from five primary care clinics delivering ART in Lusaka, Zambia. Closed surveys were conducted with 148 patients receiving ART, 29 PEs, and 53 HCWs. Data was imported into Microsoft Excel to calculate descriptive statistics. Six focus group discussions and eight key informant (KI) interviews were conducted, recorded, transcribed, and coded to extract relevant data. Survey results demonstrated that 50 of 53 (96.1%) HCWs agreed PEs reduced the amount of counseling duties required of HCWs. HCWs felt that PEs performed as well as HCWs in counseling patients (48 of 53; 90.6%) and that having PEs conduct counseling enabled clinical staff to see more patients (44 of 53; 83%). A majority of patients (141 of 148; 95.2%) agreed or strongly agreed that PEs were knowledgeable about ART, and 89 of 144 (61.8%) expressed a high level of confidence with PEs performing counseling and related tasks. Focus group and KI interviews supported these findings. PEs helped ease the work burden of HCWs and provided effective counseling, education talks, and adherence support to patients in HIV care. Consideration should be given to formalizing their role in the public health sector.Item Six-month hemoglobin concentration and its association with subsequent mortality among adults on antiretroviral therapy in Lusaka, Zambia.(2012-Sep-01) Giganti, Mark J.; Limbada, Mohammed; Mwango, Albert; Moyo, Crispin; Mulenga, Lloyd B.; Guffey, Brad M.; Mulenga, Priscilla L.; Bolton-Moore, Carolyn; Stringer, Jeffrey S.; Chi, Benjamin H.Little is known about changes in hemoglobin concentration early in the course of antiretroviral therapy and its subsequent relation to survival. We analyzed data for 40,410 HIV-infected adults on antiretroviral therapy in Lusaka, Zambia. Our main exposure of interest was 6-month hemoglobin, but we stratified our analysis by baseline hemoglobin to allow for potential effect modification. Patients with a 6-month hemoglobin <8.5 g/dL, regardless of baseline, had the highest hazard for death after 6 months (hazard ratio: 4.5; 95% confidence interval: 3.3 to 6.3). Future work should look to identify causes of anemia in settings such as ours and evaluate strategies for more timely diagnosis and treatment.Item Nonvirologic algorithms for predicting HIV infection among HIV-exposed infants younger than 12 weeks of age.(2013-Feb) Chi, Benjamin H.; Limbada, Mohammed I.; Giganti, Mark J.; Li, Michelle S.; Bweupe, Maximillian; Musonda, Patrick; Bubala, Peggy; Mubiana-Mbewe, Mwangelwa; Chintu, Namwinga T.; Bolton-Moore, Carolyn; Stringer, Jeffrey S.BACKGROUND: Early initiation of antiretroviral therapy has been shown to reduce mortality among perinatally HIV-infected infants, but availability of virologic testing remains limited in many settings. METHODS: We collected cross-sectional data from mother-infant pairs in three primary care clinics in Lusaka, Zambia, to develop predictive models for HIV infection among infants younger than 12 weeks of age. We evaluated algorithm performance for all possible combinations of selected characteristics using an iterative approach. In primary analysis, we identified the model with the highest combined sensitivity and specificity. RESULTS: Between July 2009 and May 2011, 822 eligible HIV-infected mothers and their HIV-exposed infants were enrolled; of these, 44 (5.4%) infants had HIV diagnosed. We evaluated 382,155,260 different characteristic combinations for predicting infant HIV infection. The algorithm with the highest combined sensitivity and specificity required 5 of the following 7 characteristic thresholds: infant CD8 percentage >22; infant CD4 percentage ≤44; infant weight-for-age Z score ≤0; infant CD4 ≤1600 cells/µL; infant CD8 >2200 cells/µL; maternal CD4 ≤600 cells/µL; and mother not currently using antiretroviral therapy for HIV treatment. This combination had a sensitivity of 90.3%, specificity of 78.4%, positive predictive value of 22.4%, negative predictive value of 99.2% and area under the curve of 0.844. CONCLUSION: Predicting HIV infection in HIV-exposed infants in this age group is difficult using clinical and immunologic characteristics. Expansion of polymerase chain reaction capacity in resource-limited settings remains urgently needed.