Browsing by Author "Stringer JS"

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A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.
(2010-Mar-12) Koethe JR; Westfall AO; Luhanga DK; Clark GM; Goldman JD; Mulenga PL; Cantrell RA; Chi BH; Zulu I; Saag MS; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree). METHODOLOGY: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. PRINCIPAL FINDINGS: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. CONCLUSIONS: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00929604.
A mobile phone-based, community health worker program for referral, follow-up, and service outreach in rural Zambia: outcomes and overview.
(2014-Aug) Schuttner L; Sindano N; Theis M; Zue C; Joseph J; Chilengi R; Chi BH; Stringer JS; Chintu N; 1 Centre for Infectious Disease Research in Zambia , Lusaka, Zambia .; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Mobile health (m-health) utilizes widespread access to mobile phone technologies to expand health services. Community health workers (CHWs) provide first-level contact with health facilities; combining CHW efforts with m-health may be an avenue for improving primary care services. As part of a primary care improvement project, a pilot CHW program was developed using a mobile phone-based application for outreach, referral, and follow-up between the clinic and community in rural Zambia. MATERIALS AND METHODS: The program was implemented at six primary care sites. Computers were installed at clinics for data entry, and data were transmitted to central servers. In the field, using a mobile phone to send data and receive follow-up requests, CHWs conducted household health surveillance visits, referred individuals to clinic, and followed up clinic patients. RESULTS: From January to April 2011, 24 CHWs surveyed 6,197 households with 33,304 inhabitants. Of 15,539 clinic visits, 1,173 (8%) had a follow-up visit indicated and transmitted via a mobile phone to designated CHWs. CHWs performed one or more follow-ups on 74% (n=871) of active requests and obtained outcomes on 63% (n=741). From all community visits combined, CHWs referred 840 individuals to a clinic. CONCLUSIONS: CHWs completed all planned aspects of surveillance and outreach, demonstrating feasibility. Components of this pilot project may aid clinical care in rural settings and have potential for epidemiologic and health system applications. Thus, m-health has the potential to improve service outreach, guide activities, and facilitate data collection in Zambia.
A pilot study of food supplementation to improve adherence to antiretroviral therapy among food-insecure adults in Lusaka, Zambia.
(2008-Oct-01) Cantrell RA; Sinkala M; Megazinni K; Lawson-Marriott S; Washington S; Chi BH; Tambatamba-Chapula B; Levy J; Stringer EM; Mulenga L; Stringer JS; Centre for Infectious Disease Research in Zambia, Plot 1275 Lubutu Road, Lusaka, Zambia. cantrell@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: The provision of food supplementation to food-insecure patients initiating antiretroviral therapy (ART) may improve adherence to medications. METHODS: A home-based adherence support program at 8 government clinics assessed patients for food insecurity. Four clinics provided food supplementation, and 4 acted as controls. The analysis compared adherence (assessed by medication possession ratio), CD4, and weight gain outcomes among food-insecure patients enrolled at the food clinics with those enrolled at the control clinics. RESULTS: Between May 1, 2004, and March 31, 2005, 636 food- insecure adults were enrolled. Food supplementation was associated with better adherence to therapy. Two hundred fifty-eight of 366 (70%) patients in the food group achieved a medication possession ratio of 95% or greater versus 79 of 166 (48%) among controls (relative risk = 1.5; 95% confidence interval: 1.2 to 1.8). This finding was unchanged after adjustment for sex, age, baseline CD4 count, baseline World Health Organization stage, and baseline hemoglobin. We did not observe a significant effect of food supplementation on weight gain or CD4 cell response. CONCLUSIONS: This analysis suggests that providing food to food-insecure patients initiating ART is feasible and may improve adherence to medication. A large randomized study of the clinical benefits of food supplementation to ART patients is urgently needed to inform international policy.
A population-based cohort study of stillbirth among twins in Lusaka, Zambia.
(2015-Jul) Stringer EM; Chibwesha C; Stoner M; Vwalika B; Joseph J; Chi BH; Kaunda E; Goodnight W; Stringer JS; Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: elizabeth_stringer@med.unc.edu.; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Obstetrics and Gynaecology, University Teaching Hospital, Lusaka, Zambia.; Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Clinton Health Access Initiative, Boston, MA, USA.; Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To determine rates of stillbirth and the associated risk factors for stillbirth among twins delivered in Lusaka, Zambia. METHODS: A retrospective cohort analysis was conducted of singletons and twins delivered at 26 public sector facilities between February 1, 2006, and May 31, 2013. Data were obtained from the Zambian Electronic Perinatal Record System. Risk of stillbirth was estimated using logistic regression. RESULTS: Overall, 260 657 singletons and 4021 twin pairs were included. There were 5105 stillbirths; 317 twins were stillborn. The crude stillbirth rate for twins was 39.4 per 1000 births (95% confidence interval [CI] 35.2-43.7) whereas the rate for singletons was 18.4 per 1000 births (95% CI 17.9-18.9; P<0.001). Factors associated with stillbirth among twins were increased interval between delivery (>60 minutes), low birth weight (<2500 g), birth order (being the second-born), and difference in birth weights (>30% discordance). CONCLUSION: Twins were at an increased risk of stillbirth. Improved understanding of factors associated with stillbirth in this population could help to improve perinatal outcomes globally.
A Preliminary Assessment of Rotavirus Vaccine Effectiveness in Zambia.
(2016-May-01) Beres LK; Tate JE; Njobvu L; Chibwe B; Rudd C; Guffey MB; Stringer JS; Parashar UD; Chilengi R; Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.; Centre for Infectious Disease Research in Zambia, Lusaka Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.; Centre for Infectious Disease Research in Zambia, Lusaka.; University of North Carolina School of Medicine, Chapel Hill.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: Diarrhea is the third leading cause of child death in Zambia. Up to one-third of diarrhea cases resulting in hospitalization and/or death are caused by vaccine-preventable rotavirus. In January 2012, Zambia initiated a pilot introduction of the Rotarix live, oral rotavirus vaccine in all public health facilities in Lusaka Province. METHODS: Between July 2012 and October 2013, we conducted a case-control study at 6 public sector sites to estimate rotavirus vaccine effectiveness (VE) in age-eligible children presenting with diarrhea. We computed the odds of having received at least 1 dose of Rotarix among children whose stool was positive for rotavirus antigen (cases) and children whose stool was negative (controls). We adjusted the resulting odds ratio (OR) for patient age, calendar month of presentation, and clinical site, and expressed VE as (1 - adjusted OR) × 100. RESULTS: A total of 91 rotavirus-positive cases and 298 rotavirus-negative controls who had under-5 card-confirmed vaccination status and were ≥6 months of age were included in the case-control analysis. Among rotavirus-positive children who were age-eligible to be vaccinated, 20% were hospitalized. Against rotavirus diarrhea of all severity, the adjusted 2-dose VE was 26% (95% confidence interval [CI], -30% to 58%) among children ≥6 months of age. VE against hospitalized children ≥6 months of age was 56% (95% CI, -34% to 86%). CONCLUSIONS: We observed a higher point estimate for VE against increased severity of illness compared with milder disease, but were not powered to detect a low level of VE against milder disease.
A randomized trial of the intrauterine contraceptive device vs hormonal contraception in women who are infected with the human immunodeficiency virus.
(2007-Aug) Stringer EM; Kaseba C; Levy J; Sinkala M; Goldenberg RL; Chi BH; Matongo I; Vermund SH; Mwanahamuntu M; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. eli@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: The purpose of this study was to determine whether the intrauterine contraceptive device (IUD) is effective and safe among women who are infected with the human immunodeficiency virus (HIV). STUDY DESIGN: We randomly assigned 599 postpartum, HIV-infected women in Zambia to receive either a copper IUD or hormonal contraception and followed them for at least 2 years. RESULTS: Women who were assigned randomly to hormonal contraception were more likely to become pregnant than those who were assigned randomly to receive an IUD (rate, 4.6/100 vs 2.0/100 woman-years; hazards ratio, 2.4; 95% CI, 1.3-4.7). One woman who was assigned to the IUD experienced pelvic inflammatory disease (crude rate, 0.16/100 woman-years; 95% CI, 0.004-868); there was no pelvic inflammatory disease among those women who were assigned to hormonal contraception. Clinical disease progression (death or CD4+ lymphocyte count dropping below 200 cells/microL) was more common in women who were allocated to hormonal contraception (13.2/100 woman-years) than in women who were allocated to the IUD (8.6/100 woman-years; hazard ratio, 1.5; 95% CI, 1.04-2.1). CONCLUSION: The IUD is effective and safe in HIV-infected women. The unexpected observation that hormonal contraception was associated with more rapid HIV disease progression requires urgent further study.
Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission.
(2008-Jun-01) Chi BH; Chintu N; Cantrell RA; Kankasa C; Kruse G; Mbewe F; Sinkala M; Smith PJ; Stringer EM; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission. METHODS: In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens. RESULTS: Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P = 0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR] = 0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR = 0.8, 95% CI: 0.3 to 1.8). CONCLUSIONS: Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.
Adherence to first-line antiretroviral therapy affects non-virologic outcomes among patients on treatment for more than 12 months in Lusaka, Zambia.
(2009-Jun) Chi BH; Cantrell RA; Zulu I; Mulenga LB; Levy JW; Tambatamba BC; Reid S; Mwango A; Mwinga A; Bulterys M; Saag MS; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
BACKGROUND: High-level adherence to antiretroviral therapy (ART) is associated with favourable patient outcomes. In resource-constrained settings, however, there are few validated measures. We examined the correlation between clinical outcomes and the medication possession ratio (MPR), a pharmacy-based measure of adherence. METHODS: We analysed data from a large programmatic cohort across 18 primary care centres providing ART in Lusaka, Zambia. Patients were stratified into three categories based on MPR-calculated adherence over the first 12 months: optimal (> or =95%), suboptimal (80-94%) and poor (<80%). RESULTS: Overall, 27 115 treatment-naïve adults initiated and continued ART for > or =12 months: 17 060 (62.9%) demonstrated optimal adherence, 7682 (28.3%) had suboptimal adherence and 2373 (8.8%) had poor adherence. When compared with those with optimal adherence, post-12-month mortality risk was similar among patients with sub-optimal adherence [adjusted hazard ratio (AHR) = 1.0; 95% CI: 0.9-1.2] but higher in patients with poor adherence (AHR = 1.7; 95% CI: 1.4-2.2). Those <80% MPR also appeared to have an attenuated CD4 response at 18 months (185 cells/microl vs 217 cells/microl; P < 0.001), 24 months (213 cells/microl vs 246 cells/microl; P < 0.001), 30 months (226 cells/microl vs 261 cells/microl; P < 0.001) and 36 months (245 cells/microl vs 275 cells/microl; P < 0.01) when compared with those above this threshold. CONCLUSIONS: MPR was predictive of clinical outcomes and immunologic response in this large public sector antiretroviral treatment program. This marker may have a role in guiding programmatic monitoring and clinical care in resource-constrained settings.
Advancing cervical cancer prevention initiatives in resource-constrained settings: insights from the Cervical Cancer Prevention Program in Zambia.
(2011-May) Mwanahamuntu MH; Sahasrabuddhe VV; Kapambwe S; Pfaendler KS; Chibwesha C; Mkumba G; Mudenda V; Hicks ML; Vermund SH; Stringer JS; Parham GP; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Groesbeck Parham and colleagues describe their Cervical Cancer Prevention Program in Zambia, which has provided services to over 58,000 women over the past five years, and share lessons learned from the program's implementation and integration with existing HIV/AIDS programs.
Age at antiretroviral therapy initiation predicts immune recovery, death, and loss to follow-up among HIV-infected adults in urban Zambia.
(2014-Oct) Vinikoor MJ; Joseph J; Mwale J; Marx MA; Goma FM; Mulenga LB; Stringer JS; Eron JJ; Chi BH; 1 Centre for Infectious Disease Research in Zambia , Lusaka, Zambia .; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
We analyzed the association of age at antiretroviral therapy (ART) initiation with CD4(+) T cell count recovery, death, and loss to follow-up (LTFU) among HIV-infected adults in Zambia. We compared baseline characteristics of patients by sex and age at ART initiation [categorized as 16-29 years, 30-39 years, 40-49 years, 50-59 years, and 60 years and older]. We used the medication possession ratio to assess adherence and analysis of covariance to measure the adjusted change in CD4(+) T cell count during ART. Using Cox proportional hazard regression, we examined the association of age with death and LTFU. In a secondary analysis, we repeated models with age as a continuous variable. Among 92,130 HIV-infected adults who initiated ART, the median age was 34 years and 6,281 (6.8%) were aged ≥50 years. Compared with 16-29 year olds, 40-49 year olds (-46 cells/mm(3)), 50-59 year olds (-53 cells/mm(3)), and 60+ year olds (-60 cells/mm(3)) had reduced CD4(+) T cell gains during ART. The adjusted hazard ratio (AHR) for death was increased for individuals aged ≥40 years (AHR 1.25 for 40-49 year olds, 1.56 for 50-59 year olds, and 2.97 for 60+ year olds). Adherence and retention in care were poorest among 16-29 year olds but similar in other groups. As a continuous variable, a 5-year increase in age predicted reduced CD4(+) T cell count recovery and increased risk of death. Increased age at ART initiation was associated with poorer clinical outcomes, while age <30 years was associated with a higher likelihood of being lost to follow-up. HIV treatment guidelines should consider age-specific recommendations.
An empirical approach to defining loss to follow-up among patients enrolled in antiretroviral treatment programs.
(2010-Apr-15) Chi BH; Cantrell RA; Mwango A; Westfall AO; Mutale W; Limbada M; Mulenga LB; Vermund SH; Stringer JS; Centre for Infectious Disease Research in Zambia, Box 34681, 1275 Lubuto Road, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
In many programs providing antiretroviral therapy (ART), clinicians report substantial patient attrition; however, there are no consensus criteria for defining patient loss to follow-up (LTFU). Data on a multisite human immunodeficiency virus (HIV) treatment cohort in Lusaka, Zambia, were used to determine an empirical "days-late" definition of LTFU among patients on ART. Cohort members were classified as either "in care" or LTFU as of December 31, 2007, according to a range of days-late intervals. The authors then looked forward in the database to determine which patients actually returned to care at any point over the following year. The interval that best minimized LTFU misclassification was described as "best-performing." Overall, 33,704 HIV-infected adults on ART were included. Nearly one-third (n = 10,196) were at least 1 day late for an appointment. The best-performing LTFU definition was 56 days after a missed visit, which had a sensitivity of 84.1% (95% confidence interval (CI): 83.2, 85.0), specificity of 97.5% (95% CI: 97.3, 97.7), and misclassification of 5.1% (95% CI: 4.8, 5.3). The 60-day threshold performed similarly well, with only a marginal difference (<0.1%) in misclassification. This analysis suggests that > or =60 days since the last appointment is a reasonable definition of LTFU. Standardization to empirically derived definitions of LTFU will permit more reliable comparisons within and across programs.
Antiretroviral drug regimens to prevent mother-to-child transmission of HIV: a review of scientific, program, and policy advances for sub-Saharan Africa.
(2013-Jun) Chi BH; Stringer JS; Moodley D; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@cidrz.org; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to "virtually eliminate" pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges--and opportunities--of improving health services for HIV-infected mothers and their children across the region.
Association between weight gain and clinical outcomes among malnourished adults initiating antiretroviral therapy in Lusaka, Zambia.
(2010-Apr-01) Koethe JR; Lukusa A; Giganti MJ; Chi BH; Nyirenda CK; Limbada MI; Banda Y; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. john.r.koethe@vanderbilt.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
OBJECTIVE: To describe the association between 6-month weight gain on antiretroviral therapy (ART) and subsequent clinical outcomes. DESIGN: A retrospective analysis of a large programmatic cohort in Lusaka, Zambia. METHODS: Using Kaplan-Meier analysis and Cox proportional hazards models, we examined the association between 6-month weight gain and the risk of subsequent death and clinical treatment failure. Because it is a known effect modifier, we stratified our analysis according to body mass index (BMI). RESULTS: Twenty-seven thousand nine hundred fifteen adults initiating ART were included in the analysis. Patients in the lower BMI categories demonstrated greater weight gain. In the post 6-month analysis, absolute weight loss was strongly associated with mortality across all BMI strata, with the highest risk observed among those with BMI <16 kg/m (adjusted hazard ratio 9.7; 95% CI: 4.7 to 20.0). There seemed to be an inverse relationship between weight gain and mortality among patients with BMI <16 kg/m. Similar trends were observed with clinical treatment failure. CONCLUSIONS: Weight gain after ART initiation is associated with improved survival and decreased risk for clinical failure, especially in the lower BMI strata. Prospective trials to promote weight gain after ART initiation among malnourished patients in resource-constrained settings are warranted.
Breastfeeding in HIV-positive women: What can be recommended?
(2010) Slater M; Stringer EM; Stringer JS; University of Alabama at Birmingham, Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. mackenzieslater@gmail.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Breastfeeding remains a common practice in parts of the world where the burden of HIV is highest and the fewest alternative feeding options exist. The impossible dilemma faced by HIV-positive mothers is whether to breastfeed their infants in keeping with cultural norms but in doing so risk transmitting the virus through breast milk, or to pursue formula feeding, which comes with its own set of risks, including a higher rate of infant mortality from diarrheal illnesses, while reducing transmission of HIV. Treatment of mothers and/or their infants with antiretroviral drugs is a strategy that has been employed for several decades to reduce HIV transmission through pregnancy and delivery, but the effect of these agents when taken during breastfeeding is a newer field of study. In this article we evaluate the latest clinical research, from trials that encourage exclusive breastfeeding to trials of antiretroviral therapy (ART) for either the mother or infant, in an attempt to prevent transmission of HIV through breast milk. Additionally, we discuss research that is in progress, with results anticipated in the next few years that will further shape clinical guidelines and practice. Exclusive breastfeeding is much safer than mixed feeding (the supplementation of breastfeeding with other foods), and should be encouraged even in settings where ART for either the mother or infant is not readily available. The research published regarding maternal treatment with highly active antiretroviral therapy (HAART) during pregnancy and the breastfeeding period has all been non-randomized with relatively little statistical power, but suggests maternal HAART can drastically reduce the risk of transmission of HIV. Infant prophylaxis has been intensively studied in several trials and has been shown to be as effective as maternal treatment with antiretrovirals, reducing the transmission rate after 6 weeks to as low as 1.2%. Research that is in progress will provide us with more answers about the relative contribution of maternal treatment and infant prophylaxis in preventing transmission, and the results of such research may be expected as early as this year through 2013. There is hope that perinatal HIV transmission may be greatly reduced in breastfeeding populations worldwide through a combination of behavioral interventions that encourage exclusive breastfeeding and pharmacologic interventions with antiretrovirals for mothers and/or their infants.
Causes of morbidity among HIV-infected children on antiretroviral therapy in primary care facilities in Lusaka, Zambia.
(2009-Oct) Mubiana-Mbewe M; Bolton-Moore C; Banda Y; Chintu N; Nalubamba-Phiri M; Giganti M; Guffey MB; Sambo P; Stringer EM; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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 E; Lembalemba MK; Guffey MB; Bolton-Moore C; Mubiana-Mbewe M; Chintu N; Giganti MJ; Nalubamba-Phiri M; Stringer EM; Stringer JS; Chi BH; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
CD4+ response and subsequent risk of death among patients on antiretroviral therapy in Lusaka, Zambia.
(2009-Sep-01) Chi BH; Giganti M; Mulenga PL; Limbada M; Reid SE; Mutale W; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. bchi@uab.edu; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
INTRODUCTION: Where virologic monitoring is not routinely available, immunologic criteria are commonly used to determine treatment failure while on antiretroviral therapy (ART). However, few have studied CD4+ response and its relationship to subsequent clinical outcomes in a programmatic setting. METHODS: We analyzed cohort data from Zambia to investigate whether 6- and 12-month CD4+ response after ART initiation was associated with later mortality. We used Cox proportional hazards models that accounted for different strata of baseline CD4 counts and adjusted for age, sex, clinical stage, tuberculosis coinfection, baseline hemoglobin, initial ART regimen, and adherence behavior. RESULTS: We analyzed data from 2 cohorts, from 6 months onward (n = 24,366; median follow-up = 467 days, interquartile range 222-791) and from 12 months onward (n = 17,920; median follow-up = 423 days, interquartile range 191-689). In the post-6-month analysis, hazard for death was significantly higher when absolute CD4+ response was <100 cells per microliter [adjusted hazard ratio (AHR) = 2.25, 95% confidence interval (CI): 1.91 to 2.64], relative response was <10% above baseline (AHR = 2.60, 95% CI: 2.12 to 3.19), and absolute CD4+ count was <100 per microliter (AHR = 2.79, 95% CI: 2.26 to 3.45). In the post-12 month analysis, mortality was associated with rise in absolute CD4+ cell count <200 per microliter (AHR = 2.41, 95% CI: 1.83 to 3.17), relative rise in CD4+ cell count of <10% above baseline (AHR = 3.41, 95% CI: 2.51 to 4.64), and absolute CD4+ count at 12 months <100 per microliter (AHR = 4.11, 95% CI: 2.96 to 5.68). CONCLUSION: Commonly used definitions for immunologic treatment failure are associated with elevated mortality risk among patients on ART.
Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia.
(2007-Oct-24) Bolton-Moore C; Mubiana-Mbewe M; Cantrell RA; Chintu N; Stringer EM; Chi BH; Sinkala M; Kankasa C; Wilson CM; Wilfert CM; Mwango A; Levy J; Abrams EJ; Bulterys M; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
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.
Clinical performance of digital cervicography and cytology for cervical cancer screening in HIV-infected women in Lusaka, Zambia.
(2014-Oct-01) Bateman AC; Parham GP; Sahasrabuddhe VV; Mwanahamuntu MH; Kapambwe S; Katundu K; Nkole T; Mulundika J; Pfaendler KS; Hicks ML; Shibemba A; Vermund SH; Stringer JS; Chibwesha CJ; *Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; †University of North Carolina at Chapel Hill, Chapel Hill, NC; ‡University Teaching Hospital, Lusaka, Zambia; §Vanderbilt University, Nashville, TN; ‖University of Cincinnati, Cincinnati, OH; and ¶Michigan Cancer Institute, Pontiac, MI.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Although there is a growing literature on the clinical performance of visual inspection with acetic acid in HIV-infected women, to the best of our knowledge, none have studied visual inspection with acetic acid enhanced by digital cervicography. We estimated clinical performance of cervicography and cytology to detect cervical intraepithelial neoplasia grade 2 or worse. Sensitivity and specificity of cervicography were 84% [95% confidence interval (CI): 72 to 91) and 58% (95% CI: 52 to 64). At the high-grade squamous intraepithelial lesion or worse cutoff for cytology, sensitivity and specificity were 61% (95% CI: 48 to 72) and 58% (95% CI: 52 to 64). In our study, cervicography seems to be as good as cytology in HIV-infected women.
Community-based follow-up for late patients enrolled in a district-wide programme for antiretroviral therapy in Lusaka, Zambia.
(2008-Mar) Krebs DW; Chi BH; Mulenga Y; Morris M; Cantrell RA; Mulenga L; Levy J; Sinkala M; Stringer JS; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia. dankrebs@gmail.com; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
Timely adherence to clinical and pharmacy appointments is well correlated with favourable patient outcomes among HIV-infected individuals on antiretroviral therapy. To date, however, there is little work exploring reasons behind missed visits or evaluating programmatic strategies to recall patients. For this study we implemented community-based follow-up of late patients as part of a large-scale programme for HIV care and treatment in Lusaka, Zambia. Through a network of local home-based care organizations, we attempted home visits to recall patients using locator information provided at time of enrolment. Between May and September 2005, home-based caregivers were dispatched to trace 1,343 patients with missed appointments. Of these, 554 (41%) were untraceable because the provided address was invalid, the patient had moved or no one was at the home. Of the remaining 789, 359 (46%) were reported to have died. Only 430 (54% of those traced, 32% overall) were contacted directly and encouraged to return for care. The likelihood of patient return was higher among traced patients in crude analysis (relative risk [RR] = 2.5; 95%CI = 1.9-3.2) and in multivariable analysis controlling for baseline body mass index, sex and CD4 + count < or = 50/microL (adjusted RR = 2.3; 95%CI = 1.7-3.2). However, the process was inefficient: one late patient returned for every 18 home visits that were made. Reasons for missed visits were provided in 271 of 430 (63%) of the patients who were successfully traced. Common reasons included feeling too sick to come to the clinic, travelling away from home and being too busy. Despite the availability of free ART in Lusaka, patients face significant barriers to attending scheduled clinical visits. Cost-effective and feasible strategies are urgently needed to improve timely patient follow-up.